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Modulating effects of acyl-CoA synthetase 5-derived mitochondrial Wnt2B palmitoylation on intestinal Wnt activity 被引量:6
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作者 Christina Klaus Ursula Schneider +5 位作者 Christian Hedberg Anke K Schütz Jürgen Bernhagen Herbert Waldmann Nikolaus Gassler Elke Kaemmerer 《World Journal of Gastroenterology》 SCIE CAS 2014年第40期14855-14864,共10页
AIM: To investigate the role of acyl-CoA synthetase 5 (ACSL5) activity in Wnt signaling in intestinal surface epithelia.
关键词 Acyl-CoA synthetases Wnt signaling palmitoylation Intestinal barrier CARCINOGENESIS
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Regulatory Role of Free Fatty Acids (FFAs)—Palmitoylation and Myristoylation
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作者 Chung S. Kim Ivan A. Ross 《Food and Nutrition Sciences》 2013年第9期202-211,共10页
Multicellular organisms use chemical messengers to transmit signals among organelles and to other cells. Relatively small hydrophobic molecules such as lipids are excellent candidates for this signaling purpose. In mo... Multicellular organisms use chemical messengers to transmit signals among organelles and to other cells. Relatively small hydrophobic molecules such as lipids are excellent candidates for this signaling purpose. In most proteins, palmitic acid and other saturated and some unsaturated fatty acids are esterified to the free thiol of cysteines and to the N-amide terminal. This palmitoylation process enhances the surface hydrophobicity and membrane affinity of protein substrates and plays important roles in modulating proteins’ trafficking, stability, and sorting etc. Protein palmitoylation has been involved in numerous cellular processes, including signaling, apoptosis, and neuronal transmission. The palmitoylation process is involved in multiple diseases such as Huntington’s disease, various cardiovascular and T-cell mediated immune disorders, as well as cancer. Protein palmitoylation through the thioester (S-acylation) is unique in that it is the only reversible lipid modification. Our study on lipopolysaccharide (LPS) and deoxynivalenol (DON) treatment to rats provides some insights to the complex role of protein palmitoylation in chemical and microbial toxicity. In contrast, myrisoylated proteins contain the 14-carbon fatty acid myristate attached via amide linkage to the N-terminal glycine residue of protein, and occur cotranslationally. The bacterial outer membrane enzyme lipid A palmitoyltransferase (PagP) confers resistance to host immune defenses by transferring a palmitate chain from a phospholipid to the lipid A component of LPS. PagP is sensitive to cationic antimicrobial peptides (CAMP) which are included among the products of the Toll-like receptor 4 (TLR4) signal transduction pathway. This modification of lipid A with a palmitate appears to both and protects the pathogenic bacteria from host immune defenses and attenuates the activation of those same defenses through the TLR4 signal transduction pathway. 展开更多
关键词 Free FATTY ACIDS palmitoylation MYRISTOYLATION Microbial and Chemical Toxicity INNATE Immune Response
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Understanding protein palmitoylation:Biological significance and enzymology 被引量:6
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作者 FIERKE Carol A. 《Science China Chemistry》 SCIE EI CAS 2011年第12期1888-1897,共10页
Protein palmitoylation is a widespread lipid modification in which one or more cysteine thiols on a substrate protein are modified to form a thioester with a palmitoyl group.This lipid modification is readily reversib... Protein palmitoylation is a widespread lipid modification in which one or more cysteine thiols on a substrate protein are modified to form a thioester with a palmitoyl group.This lipid modification is readily reversible;a feature of protein palmitoylation that allows for rapid regulation of the function of many cellular proteins.Mutations in palmitoyltransferases(PATs),the enzymes that catalyze the formation of this modification,are associated with a number of neurological diseases and cancer progression.This review summarizes the crucial role of palmitoylation in biological systems,the discovery of the DHHC protein family that catalyzes protein palmitoylation,and the development of methods for investigating the catalytic mechanism of PATs. 展开更多
关键词 protein palmitoylation palmitoyltransferase (PAT) DHHC protein family catalytic mechanism palmitoylation assay
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S-palmitoylation regulates AMPA receptors trafficking and function: a novel insight into synaptic regulation and therapeutics 被引量:7
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作者 Jun Han Pengfei Wu +1 位作者 Fang Wang Jianguo Chen 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2015年第1期1-7,共7页
Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translatio... Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translational modifications is one of the key elements that allow the nervous system to adapt to environment stimulations. S-palmitoylation, an important lipid modification by post-translational addition of a long-chain fatty acid to a cysteine residue, regulates AMPA receptor trafficking, which dynamically affects multiple fundamental brain functions, such as learning and memory. In vivo, S-palmitoylation is controlled by palmitoyl acyl transferases and palmitoyl thioesterases.In this review, we highlight advances in the mechanisms for dynamic AMPA receptors palmitoylation,and discuss how palmitoylation affects AMPA receptors function at synapses in recent years.Pharmacological regulation of S-palmitoylation may serve as a novel therapeutic strategy for neurobiological diseases. 展开更多
关键词 palmitoylation AMPA receptors TRAFFICKING DHHC
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Palmitoylation of MDH2 by ZDHHC18 activates mitochondrial respiration and accelerates ovarian cancer growth 被引量:6
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作者 Xuan Pei Kai-Yue Li +9 位作者 Yuan Shen Jin-Tao Li Ming-Zhu Lei Cai-Yun Fang Hao-Jie Lu Hui-Juan Yang Wenyu Wen Miao Yin Jia Qu Qun-Ying Lei 《Science China(Life Sciences)》 SCIE CAS CSCD 2022年第10期2017-2030,共14页
Epithelial ovarian cancer(EOC) exhibits strong dependency on the tricarboxylic acid(TCA) cycle and oxidative phosphorylation to fuel anabolic process.Here,we show that malate dehydrogenase 2(MDH2),a key enzyme of the ... Epithelial ovarian cancer(EOC) exhibits strong dependency on the tricarboxylic acid(TCA) cycle and oxidative phosphorylation to fuel anabolic process.Here,we show that malate dehydrogenase 2(MDH2),a key enzyme of the TCA cycle,is palmitoylated at cysteine 138(C138) residue,resulting in increased activity of MDH2.We next identify that ZDHHC18 acts as a palmitoyltransferase of MDH2.Glutamine deprivation enhances MDH2 palmitoylation by increasing the binding between ZDHHC18 and MDH2.MDH2 silencing represses mitochondrial respiration as well as ovarian cancer cell proliferation both in vitro and in vivo.Intriguingly,re-expression of wild-type MDH2,but not its palmitoylation-deficient C138 S mutant,sustains mitochondrial respiration and restores the growth as well as clonogenic capability of ovarian cancer cells.Notably,MDH2 palmitoylation level is elevated in clinical cancer samples from patients with high-grade serous ovarian cancer.These observations suggest that MDH2 palmitoylation catalyzed by ZDHHC18 sustains mitochondrial respiration and promotes the malignancy of ovarian cancer,yielding possibilities of targeting ZDHHC18-mediated MDH2 palmitoylation in the treatment of EOC. 展开更多
关键词 EOC MDH2 cysteine palmitoylation ZDHHC18 GLUTAMINE
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STING palmitoylation as a therapeutic target 被引量:5
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作者 Anne Louise Hansen Kojiro Mukai +2 位作者 Francisco J.Schopfer Tomohiko Taguchi Christian K.Holm 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2019年第3期236-241,共6页
Gain-of-function mutations in the STING-encoding gene TMEM173 are central to the pathology of the autoinflammatory disorder STING-associated vasculopathy with onset in infancy(SAVI).Furthermore,excessive activity of t... Gain-of-function mutations in the STING-encoding gene TMEM173 are central to the pathology of the autoinflammatory disorder STING-associated vasculopathy with onset in infancy(SAVI).Furthermore,excessive activity of the STING signaling pathway is associated with autoinflammatory diseases,including systemic lupus erythematosus and Aicardi–Goutières syndrome(AGS).Two independent studies recently identified pharmacological inhibitors of STING.Strikingly,both types of compounds are reactive nitrocontaining electrophiles that target STING palmitoylation,a posttranslational modification necessary for STING signaling.As a consequence,the activation of downstream signaling molecules and the induction of type I interferons were inhibited.The compounds were effective at ameliorating inflammation in a mouse model of AGS and in blocking the production of type I interferons in primary fibroblasts from SAVI patients.This mini-review focuses on the roles of palmitoylation in STING activation and signaling and as a pharmaceutical target for drug development. 展开更多
关键词 STING palmitoylation INFLAMMATION SAVI Interferonopathies
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Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3 被引量:2
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作者 Tian Lu Yong Li +18 位作者 Wenchao Lu TWGM Spitters Xueyu Fang Jun Wang Simian Cai Jing Gao Yanting Zhou Zhe Duan Huan Xiong Liping Liu Qi Li Hualiang Jiang Kaixian Chen Hu Zhou Hua Lin Huijin Feng Bing Zhou Christopher L.Antos Cheng Luo 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2021年第10期3206-3219,共14页
The TEA domain(TEAD)family proteins(TEAD1-4)are essential transcription factors that control cell differentiation and organ size in the Hippo pathway.Although the sequences and structures of TEAD family proteins are h... The TEA domain(TEAD)family proteins(TEAD1-4)are essential transcription factors that control cell differentiation and organ size in the Hippo pathway.Although the sequences and structures of TEAD family proteins are highly conserved,each TEAD isoform has unique physiological and pathological functions.Therefore,the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases.Here,we identified a novel TEAD 1/3 covalent inhibitor(DC-TEADin1072)with biochemical IC50 values of 0.61±0.02 and 0.58±0.12μmol/L against TEAD1 and TEAD3,respectively.Further chemical optimization based on DC-TEAD in 1072 yielded a selective TEAD3 inhibitor DCTEAD3 in03 with the IC_(50) value of 0.16±0.03μmol/L,which shows 100-fold selectivity over other TEAD isoforms in activity-based protein profiling(ABPP)assays.In cells,DC-TEAD3 in03 showed selective inhibitory effect on TEAD3 in GAL4-TEAD(1-4)reporter assays with the IC50 value of1.15μmol/L.When administered to zebrafish juveniles,experiments showed that DC-TEAD3 in03 reduced the growth rate of zebrafish caudal fins,indicating the importance of TEAD3 activity in controlling proportional growth of vertebrate appendages. 展开更多
关键词 Hippo pathway TEAD3 Covalent inhibitor palmitoylation inhibitor
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In vitro palmitoylation of native bovine brain G_oα 被引量:1
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作者 杨胜于 黄有国 《Science China(Life Sciences)》 SCIE CAS 2000年第5期482-488,共7页
The native Goα was purified from bovine brain cortex and palmitoylated in vitro. The in vitro palmitoylation site was the same as that in vivo. The internal palmitoylation of purified native Goα was found to be larg... The native Goα was purified from bovine brain cortex and palmitoylated in vitro. The in vitro palmitoylation site was the same as that in vivo. The internal palmitoylation of purified native Goα was found to be largely maintained. The apparent palmitoylation ratio was significantly increased after the Goα was treated with DTT. The GTPγS binding characteristic of Goα was not influenced by palmitoylation, however, the affinity for LUVs was increased dramatically. The in vitro palmitoylation model of Goα provides a better basis for studying the functional role of G protein palmitoylation in signal transduction. 展开更多
关键词 NATIVE Goα in VITRO palmitoylation SPECIFICITY GTPγS binding activity signal transduction.
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ACSL5,a prognostic factor in acute myeloid leukemia,modulates the activity of Wnt/β-catenin signaling by palmitoylation modification 被引量:1
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作者 Wenle Ye Jinghan Wang +13 位作者 Jiansong Huang Xiao He Zhixin Ma Xia Li Xin Huang Fenglin Li Shujuan Huang Jiajia Pan Jingrui Jin Qing Ling Yungui Wang Yongping Yu Jie Sun Jie Jin 《Frontiers of Medicine》 SCIE CSCD 2023年第4期685-698,共14页
Acyl-CoA synthetase long chain family member 5(ACSL5),is a member of the acyl-CoA synthetases(ACSs)family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs.The dysregulation of ACSL5... Acyl-CoA synthetase long chain family member 5(ACSL5),is a member of the acyl-CoA synthetases(ACSs)family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs.The dysregulation of ACSL5 has been reported in some cancers,such as glioma and colon cancers.However,little is known about the role of ACSL5 in acute myeloid leukemia(AML).We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors.ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients.In AML cells,the ACSL5 knockdown inhibited cell growth both in vitro and in vivo.Mechanistically,the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a.Additionally,triacsin c,a pan-ACS family inhibitor,inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199,the FDA approved BCL-2 inhibitor for AML therapy.Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML. 展开更多
关键词 acute myeloid leukemia acyl-CoA synthetase long chain family member 5 WNT3A palmitoylation ABT-199
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Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal melanoma
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作者 Yan Zhang Baoyuan Zhang +9 位作者 Yongyun Li Yuting Dai Jiaoyang Li Donghe Li Zhizhou Xia Jianming Zhang Ping Liu Ming Chen Bo Jiao Ruibao Ren 《Frontiers of Medicine》 SCIE CSCD 2022年第5期784-798,共15页
More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane associ... More than 85%of patients with uveal melanoma(UM)carry a GNAQ or GNA11 mutation at a hotspot codon(Q209)that encodes G proteinαsubunit q/11 polypeptides(Gα_(q/11)).GNAQ/11 relies on palmitoylation for membrane association and signal transduction.Despite the palmitoylation of GNAQ/11 was discovered long before,its implication in UM remains unclear.Here,results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells.Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^(Q209L)-induced malignant transformation in NIH3T3 cells.Importantly,the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells,which are much more dependent on Gα_(q/11) signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations.Furthermore,the palmitoylation inhibitor,2-bromopalmitate,also specifically disrupted Gα_(q/11) downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor,ABT-199,in vitro.The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM. 展开更多
关键词 uveal melanoma mutant GNAQ/11 palmitoylation BCL2 combination target therapy
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Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system 被引量:1
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作者 Steinunn Sara Helgudóttir Anne Skøttrup Mørkholt +7 位作者 Jacek Lichota Preben Bruun-Nyzell Mads Christian Andersen Nanna Marie Juhl Kristensen Amanda Krøger Johansen Mikela Reinholdt Zinn Hulda Maria Jensdóttir John Dirk Vestergaard Nieland 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第7期1437-1445,共9页
Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzhe... Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements. 展开更多
关键词 brain disease carnitine palmitoyl transferase 1 EPIGENETICS metabolism gut microbiome mitochondrial dysfunction NEURODEGENERATION oxidative stress
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Carnitine palmitoyltransferase-II inactivity promotes malignant progression of metabolic dysfunction-associated fatty liver disease via liver cancer stem cell activation
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作者 Ling-Ling Wang Yu-Ming Lu +5 位作者 Yi-Han Wang Yi-Fan Wang Rong-Fei Fang Wen-Li Sai Deng-Fu Yao Min Yao 《World Journal of Gastroenterology》 SCIE CAS 2024年第47期5055-5069,共15页
BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)is one of the main chronic liver diseases.However,the roles of mitochondrial carnitine palmitoyl transferase-II(CPT-II)downregulation and liver can... BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)is one of the main chronic liver diseases.However,the roles of mitochondrial carnitine palmitoyl transferase-II(CPT-II)downregulation and liver cancer stem cell(LCSC)activation remain to be identified.AIM To investigate the dynamic alterations in CPT-II inactivity and LCSC activation during the malignant progression of MAFLD.METHODS Dynamic models of mouse MAFLD were generated via the consumption of a high-fat diet or the addition of 2-fluorenylacetamide for hepatocarcinogenesis.The mice were divided into groups on the basis of hematoxylin and eosin staining.Biochemistries,CPT-II,intrahepatic T cells,and LCSCs were determined and confirmed in clinical samples.The mitochondrial membrane potential(MMP)was analyzed.Differentially expressed genes were screened via RNA sequencing and enriched in KEGG pathways or GO functions.RESULTS Dynamic models of MAFLD malignant transformation were successfully generated on the basis of pathological examination.Hepatic lipid accumulation was associated with the loss of mitochondrial CPT-II activity and alterations in the MMP,with decreases in liver CD3+or CD4+T cells and increased AFP levels.In the lipid accumulation microenvironment,mitochondrial CPT-II was inactivated,followed by aberrant activation of CD44+or CD24+LCSCs,as validated in MAFLD or hepatocellular carcinoma patient samples.In terms of mechanism,the biological process category focused mainly on the metabolic regulation of cells in response to external stimuli.The enriched molecular functions included protein binding,cell apoptosis,and cell proliferation.CONCLUSION CPT-II inactivity promotes the malignant progression of MAFLD via the loss of innate immune function and abnormal LCSC activation. 展开更多
关键词 Metabolic dysfunction-associated fatty liver disease Carnitine palmitoyl transferase-II Mitochondria T lymphocytes Liver cancer stem cells
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Case Report: Carnitine Palmitoyl Transferase II (CPT II) Deficiency
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作者 Kathy Po Marius Chivu +1 位作者 Edwin Rosas Balpreet Kaur 《Open Journal of Internal Medicine》 2024年第1期93-101,共9页
Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting... Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting and the accumulation of the long chain fatty in the body. There are three types of CPT II deficiency, the myopathic form, the severe infantile hepatocardiomuscular form and the lethal neonatal form. They are all inherited as an autosomal recessive. Diagnosis of the CPTII are 1) tandem mass spectrometry (MS/MS) in adult form and 2) CPTII polymorphism (F352C), which is linked to reducing the activity of CPTII in infantile form [1]. Glucose is the primary management and medium-chain fatty acid is an alternative due to the bypass of the CPTII enzyme in the pathway. For the prevention of CPTII deficiency are to avoid long chain fatty acid (C12-fatty acid), fasting, prolonged exercise, known triggers, and certain medications such as anti-epileptics and general anesthesia. During the rhabdomyolysis and myoglobinuria attack, it is very important to maintain hydration to avoid acute renal failure. If, however, renal failure occurs, dialysis is recommended. We present a case of a 27-year-old African American woman with the significant past medical history of CPT II deficiency leading to recurrent rhabdomyolysis and myoglobinuria. Together with all the research studies from diagnosis to treatment of CPTII deficiency will help in clinical management of patients. And this case report will add to the existing case reports of patients who have CPTII deficiency in terms of how we diagnose, how we treat, and how we prevent symptoms from re-occurring. 展开更多
关键词 Carnitine Palmitoyl Transferase II (CPTII) Mitochondria Long Chain Fatty Acid Medium Chain Fatty Acid CARNITINE Carnitine Palmitoyl Transferase I (CPTI) Acyl-Carnitine BETA-OXIDATION RHABDOMYOLYSIS Myoglobinuria Renal Failure Hypoketotic Hypoglycemia
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Mutational analysis of hepatitis E virus ORF1 'Y-domain' : Effects on RNA replication and virion infectivity 被引量:1
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作者 Mohammad Khalid Parvez 《World Journal of Gastroenterology》 SCIE CAS 2017年第4期590-602,共13页
AIMTo investigate the role of non-structural open reading frame 1 &#x0201c;Y-domain&#x0201d; sequences in the hepatitis E virus (HEV) life cycle.METHODSSequences of human HEV Y-domain (amino acid sequences 216... AIMTo investigate the role of non-structural open reading frame 1 &#x0201c;Y-domain&#x0201d; sequences in the hepatitis E virus (HEV) life cycle.METHODSSequences of human HEV Y-domain (amino acid sequences 216-442) and closely-related viruses were analyzed in silico. Site-directed mutagenesis of the Y-domain (HEV SAR55) was carried out and studied in the replicon-baculovirus-hepatoma cell model. In vitro transcribed mRNA (pSK-GFP) constructs were transfected into S10-3 cells and viral RNA replicating GFP-positive cells were scored by flow cytometry. Mutant virions&#x02019; infectivity was assayed on na&#x000ef;ve HepG2/C3A cells.RESULTSIn silico analysis identified a potential palmitoylation-site (C<sub>336</sub>C<sub>337</sub>) and an &#x003b1;-helix segment (L<sub>410</sub>Y<sub>411</sub>S<sub>412</sub>W<sub>413</sub>L<sub>414</sub>F<sub>415</sub>E<sub>416</sub>) in the HEV Y-domain. Molecular characterization of C<sub>336</sub>A, C<sub>337</sub>A and W<sub>413</sub>A mutants of the three universally conserved residues showed non-viability. Further, of the 10 consecutive saturation mutants covering the entire Y-domain nucleotide sequences (nts 650-1339), three constructs (nts 788-994) severely affected virus replication. This revealed the indispensability of the internal sequences but not of the up- or downstream sequences at the transcriptional level. Interestingly, the three mutated residues corresponded to the downstream codons that tolerated saturation mutation, indicating their post-translational functional/structural essentiality. In addition, RNA secondary structure prediction revealed formation of stable hairpins (nts 788-994) where saturation mutation drastically inhibited virion infectivity.CONCLUSIONThis is the first demonstration of the critical role of Y-domain sequences in HEV life cycle, which may involve gene regulation and/or membrane binding in intracellular replication complexes. 展开更多
关键词 Hepatitis E virus Open reading frame 1 Y-domain palmitoylation α -HELIX
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Role of Free Fatty Acids in Physiological Conditions and Mitochondrial Dysfunction 被引量:1
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作者 Zbigniew K. Binienda Sumit Sarkar +1 位作者 Sonia Silva-Ramirez Carmen Gonzalez 《Food and Nutrition Sciences》 2013年第9期6-15,共10页
The role of free fatty acids (FFAs) as a source of energy and their functions in energy transport within the body are well established. Equally important is a role that FFAs play in oxidative stress following cell mem... The role of free fatty acids (FFAs) as a source of energy and their functions in energy transport within the body are well established. Equally important is a role that FFAs play in oxidative stress following cell membrane depolarization. FFAs are physiologically active, not only as nutritional components, but also as molecules involved in cell signaling and stabilization of membranes via palmitoylation and myristoylation. Protein palmitoylation is involved in numerous cellular processes, including apoptosis, and neuronal transmission. Besides nuclear peroxisome proliferator-activated receptors that mediate the biological effects of FFAs, G protein-coupled receptors (GPCRs) that are activated by FFA, have been recently identified. Those multiple FFA receptors (FFARs), which function on the cell surface as activated FFAs, play significant roles in the regulation of energy metabolism and mediate a wide range of important metabolic processes. FFARs have been targeted in drug development for the treatment of type 2 diabetes and metabolic syndrome. FFAs upregulate transcription of uncoupling proteins, increasing their expression in brain, cardiac, and skeletal muscle that may be protective or cytotoxic, depending on the cellular energy state. Recently, FFA effects on the endothelial function and dysfunction are being recognized. FFAs play a key role in endothelium-dependent nitric oxide production. A disturbance of endothelial function, due to an imbalance in production and release of relaxing and constricting factors, has implications in the development of cardiovascular problems, such as hypertension, as well as neurotoxicity following loss of blood-brain barrier integrity. This review presents information on broad range of FFAs actions of prime importance for physiological processes. Understanding of FFA functions in the body is crucial for developing new therapeutic strategies against several metabolic disorders. 展开更多
关键词 Free FATTY ACIDS BETA-OXIDATION MYRISTOYLATION palmitoylation ENDOTHELIUM
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Mitochondrial carnitine palmitoyl transferase-Ⅱ inactivity aggravates lipid accumulation in rat hepatocarcinogenesis 被引量:8
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作者 Juan-Juan Gu Min Yao +5 位作者 Jie Yang Yin Cai Wen-Jie Zheng Li Wang Deng-Bing Yao Deng-Fu Yao 《World Journal of Gastroenterology》 SCIE CAS 2017年第2期256-264,共9页
AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal... AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes. 展开更多
关键词 Fatty liver Carnitine palmitoyl transferaseⅡ Malignant transformation of hepatocytes Dynamic expression Rat model
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Demethylation of miR-34a upregulates expression of membrane palmitoylated proteins and promotes the apoptosis of liver cancer cells 被引量:5
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作者 Fu-Yong Li Ting-Yong Fan +1 位作者 Hao Zhang Yu-Min Sun 《World Journal of Gastroenterology》 SCIE CAS 2021年第6期470-486,共17页
BACKGROUND Liver cancer is a common cancer and the main cause of cancer-related deaths worldwide.Liver cancer is the sixth most common cancer in the world.Although miR-34a and palmitoyl membrane palmitoylated protein(... BACKGROUND Liver cancer is a common cancer and the main cause of cancer-related deaths worldwide.Liver cancer is the sixth most common cancer in the world.Although miR-34a and palmitoyl membrane palmitoylated protein(MPP2)are reportedly involved in various cell processes,their precise roles in liver cancer are still unclear.AIM To investigate the expression of micro RNA 34a(miR-34a),methylation of the miR-34a promoter and the expression of MPP2 in liver cancer cells and their related mechanisms.METHODS Together,78 cases of liver cancer tissues and 78 cases of adjacent tissues were collected.The methylation degree of miR-34a promoter in liver cancer/paracancerous tissue and liver cancer cells/normal liver cells,and the expression levels of miR-34a and MPP2 in the above samples were detected.Demethylation of liver cancer cells or transfection of liver cancer cells with miR-34a mimetic was performed.The MPP2 overexpression vector was used to transfect liver cancer cells,and the changes in proliferation,invasion,apoptosis,migration,and other biological functions of liver cancer cells after the above interventions were observed.Double luciferase reporter genes were used to detect the targeting relationship between miR-34a and MPP2.RESULTS Clinical samples showed that the expression levels of miR-34a and MPP2 in liver cancer tissues were lower than those in the normal tissues.The methylation degree of miR-34a promoter region in liver cancer cells was higher than that in normal liver cells.After miR-34a demethylation/mimetic transfection/MPP2 overexpression,the apoptosis of liver cancer cells was increased;the proliferation,invasion and migration capabilities were decreased;the expression levels of caspase 3,caspase 9,E-cadherin,and B-cell lymphoma 2(Bcl-2)-associated X protein were increased;and the expression levels of Bcl-2,N-cadherin,andβ-catenin were decreased.Double luciferase reporter genes confirmed that MPP2 is targeted by miR-34a.Rescue experiments showed that small interfering MPP2 could counteract the promoting effect of miR-34a demethylation on apoptosis and the inhibitory effect on cell proliferation,invasion,and migration.CONCLUSION miR-34a demethylation upregulates the expression level of MPP2 in liver cancer cells and promotes the apoptosis of liver cancer cells.miR-34a demethylation is a potential method for liver cancer treatment. 展开更多
关键词 Liver cancer MIR-34A Membrane palmitoylated proteins Methylation Cell apoptosis Caspase 3
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The Flow of Information from Nucleus to Golgi Is Contingent upon Nuclear Membrane Synthesis and Protraction of the Ceramide-Containing Membrane to Endoplasmic Reticulum 被引量:1
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作者 Amalia Slomiany Bronislaw L. Slomiany 《Advances in Biological Chemistry》 2018年第3期47-68,共22页
The nucleus-initiated augmentation of ER membrane is reflected in a coordinated synthesis and intercalation of the explicit proteins and lipids required for the replacement, repair and function of the cell and its org... The nucleus-initiated augmentation of ER membrane is reflected in a coordinated synthesis and intercalation of the explicit proteins and lipids required for the replacement, repair and function of the cell and its organelles. The direct connection between nucleus and the membranes containing labeled sphingosine (SphN) and ceramide (Cer) was affirmed by determining synthetic activity of serine palmitoyltransferase (SPT). The SPT and the newly synthesized serine-labeled lipid products were identified in the Outer- and Inner-Nuclear Membrane (ONM, INM) and ER. The pulse-chase experiments disclosed that the incorporation of radiolabeled lipids into both nuclear membranes declined upon their simultaneous increase in Endoplasmic Reticulum (ER). These results, and prior findings regarding metabolic transfer of nuclear membrane phosphoinositides to the outer leaflet of ER [Slomiany and Slomiany, Health, 2011, 3, 187-199], allowed us to reason that INM and ONM are not distinct entities, but uninterrupted continuum facing nucleosol and then cytosol when protracted into segment known as ER. Consequently, the identification of SPT and its products in the inner leaflet of nuclear and ER microsomes lent credence to the luminal presence of Cer in Golgi, luminal synthesis of glycosphingolipids (GSphLs), sphingomyelin (SM), and their delivery to the outer leaflet of apical and basolateral cell membrane, respectively. The findings presented in this communication provide further support to our concept that the factual intercalation of proteins and lipids into the cell membranes can only take place during their simultaneous synthesis that is guided by the nuclear and cytosolic processes enacted in nuclear-ER membrane continuum. At the nuclear stage, the signal-specific genes expression promotes active synthesis and intercalation of lipids into the organelles’ customized membrane that is protracted and articulated in ER in form of transport vesicles. 展开更多
关键词 NUCLEUS MEMBRANE Biogenesis GOLGI Secretory Pathway Serine Palmitoyl TRANSFERASE CERAMIDES SYNTHESIS in Nuclear MEMBRANE Organelle-Customized ER Transport Vesicles
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Mitochondrial carnitine palmitoyltransferase-Ⅱ dysfunction: A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis
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作者 Min Yao Ping Zhou +2 位作者 Yan-Yan Qin Li Wang Deng-Fu Yao 《World Journal of Gastroenterology》 SCIE CAS 2023年第12期1765-1778,共14页
Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseas... Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world.The complex mechanisms of NAFLD formation are still under identification.Carnitine palmitoyltransferase-Ⅱ(CPT-Ⅱ)on inner mitochondrial membrane(IMM)regulates long chain fatty acidβ-oxidation,and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD.The sequences of its peptide chain and DNA nucleotides have been identified,and the catalytic activity of CPT-Ⅱ is affected on its gene mutations,deficiency,enzymatic thermal instability,circulating carnitine level and so on.Recently,the CPT-Ⅱ dysfunction has been discovered in models of liver lipid accumulation.Meanwhile,the malignant transformation of hepatocyte-related CD44^(+) stem T cell activation,high levels of tumor-related biomarkers(AFP,GPC3)and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology.This review focuses on some of the progress of CPT-Ⅱ inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis. 展开更多
关键词 Carnitine palmitoyl transferase-II Nonalcoholic fatty liver disease Fatty acidβ-oxidation CARNITINE Hepatocyte malignant transformation Mitochondrial membrane
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Characterization and Property of Palmitoylated Konjac Glucomannan
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作者 Tian Bingshou,Dong Changming Department of Chemistry, Wuhan University, Wuhan 430072, China 《Wuhan University Journal of Natural Sciences》 CAS 1997年第4期89-92,共4页
Various degrees of palmitoylated konjac glucomannan (PKGM) are prepared by heterogeneous method. Differential thermal analysis (DTA) thermographs show PKGM having certain degree of substitution (DS) gave a new crystal... Various degrees of palmitoylated konjac glucomannan (PKGM) are prepared by heterogeneous method. Differential thermal analysis (DTA) thermographs show PKGM having certain degree of substitution (DS) gave a new crystalline peak at higher temperature. And PKGM having higher DS only shows the new crystalline state. Furthermore, the effect of the DS of PKGM on its emulsifying ability has been investigated in the water in oil(w/o) and oil in water(o/w) systems. It is demonstrated that it is a kind of good w/o emulsifier with the DS ranged between 1.00 and 1.70; Whereas for DS<0.50, It is a kind of good o/w emulsifier and an interesting phenomenon appears in o/w system. And the half time of emulsion turbidity is more than 1.5 h with PKGM having 2.72 of DS used as the emulsifier. 展开更多
关键词 palmitoylated konjac glucomannan polysaccharide emulsifier emulsifying property
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