Choline is a crucial factor in the regulation of sperm membrane structure and fluidity, and this nutrient plays an important role in the maturation and fertilizing capacity of spermatozoa. Transcripts of phosphatidyle...Choline is a crucial factor in the regulation of sperm membrane structure and fluidity, and this nutrient plays an important role in the maturation and fertilizing capacity of spermatozoa. Transcripts of phosphatidylethanolamine N-methyltransferase (PEMT) and choline dehydrogenase (CHDH), two basic enzymes of choline metabolism, have been observed in the human testis, demonstrating their gene expression in this tissue. In the present study, we explored the contribution of the PEMTand CHDHgene variants to sperm parameters. Two hundred oligospermic and 250 normozoospermic men were recruited. DNA was extracted from the spermatozoa, and the PEMT -774G〉C and CHDH +432G〉T polymorphisms were genotyped. The genotype distribution of the PEMT-774G〉C polymorphism did not differ between oligospermic and normozoospermic men. In contrast, in the case of the CHDH +432G〉T polymorphism, oligospermic men presented the CHDH432GIG genotype more frequently than normozoospermic men (62% vs. 42%, P〈0.001). The PEMT774GIG genotype was associated with a higher sperm concentration compared to the PEMT774GIC and 774C/C genotypes in oligospermic men (12.5±5.6× 10^6 spermatozoa m1-1 vs. 8.3±5.2×10^6 spermatozoa m1-1, P〈0.002) and normozoospermic men (81.5±55.6×10^6 vs. 68.1±44.5×10^6 spermatozoa m1-1, P〈0.006). In addition, the CHDH432G/G genotype was associated with higher sperm concentration compared to CHDH432G.T and 432T/T genotypes in oligospermic (11.8±5.1×10^6 vs. 7.8±5.3×10^6 spermatozoa m1-1, P〈0.003) and normozoospermic men (98.6±62.2×10^6 vs. 58.8±+33.6×10^6 spermatozoa m1-1, P〉0.001). In our series, the PEMT-774G〈C and CHDH +432G〈T polymorphisms were associated with sperm concentration. This finding suggests a possible influence of these genes on sperm quality.展开更多
AIM: To analyse the role of two common polymorphisms in genes coding for histamine metabolising enzymes as it relates to the risk to develop ulcerative colitis (UC) and the clinical course of these patients. METHOD...AIM: To analyse the role of two common polymorphisms in genes coding for histamine metabolising enzymes as it relates to the risk to develop ulcerative colitis (UC) and the clinical course of these patients. METHODS: A cohort of 229 unrelated patients with UC recruited from a single centre and 261 healthy volunteers were analysed for the presence of Thr105Ile and His645Asp amino acid substitutions at histamine N-methyltransferase (HNMT) and diamine oxidase (ABP1) enzymes, respectively, by amplification-restriction procedures. All patients were phenotyped and followed up for at least 2 years (mean time 11 years). RESULTS: There were no significant differences in the distribution of ABP1 alleles between ulcerative colitis patients and healthy individuals [OR (95% CI) for variant alleles = 1.22 (0.91-1.61)]. However, mutated ABP1 alleles were present with higher frequency among the 58 patients that required immunosuppresive drugs [OR (95 % CI) for carriers of mutated alleles 2.41 (1.21-4.83; P=0.006)], with a significant gene-dose effect (P= 0.0038). In agreement with the predominant role of ABP1 versus HNMT on local histamine metabolism in human bowel, the frequencies for carriers of HNMT genotypes or mutated alleles were similar among patients,regardless clinical evolution, and control individuals. CONCLUSION: The His645Asp polymorphism of the histamine metabolising enzyme ABP1 is related to severity of ulcerative colitis.展开更多
s Oxidative stress is involved in the progression of neurodegenerative diseases.Previous evidences showed that plasma-logens could improve neurodegenerative diseases.In this study,we investigated the function of phosp...s Oxidative stress is involved in the progression of neurodegenerative diseases.Previous evidences showed that plasma-logens could improve neurodegenerative diseases.In this study,we investigated the function of phosphoethanolamine plasmalogens enriched with EPA(EPA-pPE)and phosphatidylethanolamine enriched with EPA(EPA-PE)on oxidative damage prevention after hy-drogen peroxide(H2O2)and tert-butylhydroperoxide(t-BHP)challenge in primary hippocampal neurons.Results showed that neurons pretreated with EPA-pPE and EPA-PE demonstrated the ability to alleviate oxidative damage,which was proved by the in-creased cell viability.Moreover,the shape and number of neurons were more similar to those of the control group.Antioxidant acti-vity,apoptosis,as well as TrkB/ERK/CREB signaling pathway were investigated to explore the mechanisms.The results suggested that EPA-PE was superior to EPA-pPE in regulating mitochondrial apoptosis.EPA-pPE was more prominent than EPA-PE in upre-gulating TrkB/ERK/CREB signaling pathway.Phospholipids with EPA exerted neuroprotective effects via inhibiting oxidative stress,suppressing apoptosis,and regulating TrkB/ERK/CREB signaling pathway.Therefore,the results provide a scientific basis for utili-zation of phospholipids enriched with EPA on the treatment of neurodegenerative disease.展开更多
Background:Leukemia is a type of cancer that starts in the blood or blood-forming tissues.It results from the clonal proliferation of hematopoietic cells in the bone marrow and/or lymphoid tissues,which subsequently r...Background:Leukemia is a type of cancer that starts in the blood or blood-forming tissues.It results from the clonal proliferation of hematopoietic cells in the bone marrow and/or lymphoid tissues,which subsequently reach the peripheral circulation and can infiltrate other systems.There are many different kinds of leukemia,and treatments are different for each one.Chronic leukemia is with a slower growing than acute leukemia but could be just as life-threatening.Phospholipids are antitumor analogs,such as synthetic phosphoethanolamine,which is a phosphorylated compound capable of controlling cellular proliferation and inducing apoptosis in several types of tumor cells.Methods:K562 and K562-Lucena(MDR+)human chronic myeloid leukemia cells were treated with synthetic phosphoethanolamine(Pho-s).The viability was evaluated by sulforhodamine B(SRB)assay and cell cycle phases,apoptosis,markers expression,and mitochondrial potential were assessed by flow cytometry.Results:Tumor cells formed clusters in suspension and decreased significantly viability.The concentrations for IC50%were obtained.Pho-s treated were 43.1 mM(K562)and 145.9 mM(K562-Lucena MDR+)in a period of 24 hours.Pho-s induced changes in the distribution of cell population phases of cell cycle which showed an increase in fragmented DNA and increased markers expression envolved apoptosis pathways a decrease in the G1/G0 phase.Discussion:Treatment of K562 and K562-Lucena(MDR+)chronic myeloid leukemia cells with Pho-s showed dose and time dependent cytotoxic effects.This cytotoxicity induced a decrease in proliferative capacity,mitochondrial electrical potential,and consequently release of cytochrome C;inhibition of Bcl-2 family protein expression,increase in pro-apoptotic family members Bad and Bax,dependent on p53 expression.Conclusion:This study presented a significant therapeutic potential of Phos-s in this type of leukemia through the apoptotic effects on tumor cells independently of the molecular resistance profile(MDR+).展开更多
Synthetic phosphoethanolamine(Pho-s)is a monophosphoester ester with anti-inflammatory and pro-apoptotic properties.Meclizine chloridrate(MC)is a histamine H1 receptor blocker that is also able to inhibit cellular res...Synthetic phosphoethanolamine(Pho-s)is a monophosphoester ester with anti-inflammatory and pro-apoptotic properties.Meclizine chloridrate(MC)is a histamine H1 receptor blocker that is also able to inhibit cellular respiration.However,MC does not inhibit cellular respiration in isolated mitochondria such as antimycin and rotenone.Methyl-β-cyclodextrin(MβCD)belongs to theβ-cyclodextrin family,which is capable of removing cholesterol from the plasma membrane.The aim of this study was to evaluate the proliferative effects of meclizine chloridrate and methyl-β-cyclodextrin compounds associated with synthetic phosphoethanolamine in a triple-negative human breast tumor line,MDA-MB-231 Cell viability of the tumor line and normal cells FN1 was evaluated by MTT colorimetric test;the production of free radicals was determined by lipoperoxidation(LPO)test;and the percentage of cell cycle phases and proliferative index was evaluated by flow cytometry.Cell viability demonstrated a significant decrease with the treatments of MβCD,MC and Pho-s associated with MC.The production of free radicals decreases significantly in all treatments.In addition,a significant increase of DNA fragment and decrease in G0/G1 cell cycle phase were observed in cellular percentage with concentrations of 20 and 30 mM of Pho-s in association with MC and MβCD,respectively.展开更多
Cellular metabolism-induced epigenetic regulation is essential for the maintenance of cellular homeostasis.Nicotinamide N-methyltransferase(NNMT)is emerging as a key point of intersection between cellular metabolism a...Cellular metabolism-induced epigenetic regulation is essential for the maintenance of cellular homeostasis.Nicotinamide N-methyltransferase(NNMT)is emerging as a key point of intersection between cellular metabolism and epigenetic regulation and has a central role in various physiological and pathological processes.NNMT catalyzes the methylation of nicotinamide(NAM)using the universal methyl donor S-adenosyl methionine(SAM)to yield S-adeno-syl-L-homocysteine(SAH)and N1-methylnicotinamide(MNAM),directly linking methylation balance with nicotinamide adenosine dinucleotide(NAD+)contents.NNMT acts on either the SAM-methylation balance or both NAD+metabolism,depending on the tissue involved or pathological settings where metabolic demand is increased.Under physiological conditions,the liver act as an essential metabolic organ with abundant NNMT expression,while NNMT hepatic function is not mediated by its methyltransferase activity due to other major methyltransferases such as glycine N-methyltransferase(GNMT)in the liver.However,hepatic NNMT,as well as its metabolite is improperly regulated and linked to the worse pathological states in liver diseases,including alcoholic liver disease,non-alcoholic fatty liver disease(NAFLD),liver cirrhosis,and hepatocellular carcinoma(HCC),suggesting a potential role in the process of liver diseases.In this review,we summarize how NNMT regulates cell methylation balance and NAD metabolism,and extensively outline the current knowledge concerning the functions of NNMT in hepatic metabolism including glucose,lipid and energy,with a specific focus on the contribution of NNMT to the pathophysiology of liver-related diseases.NNMT is involved in the development and progression of liver diseases.Understanding the complex NNMT regulatory network and its effects on pathogenesis could provide new therapeutic strategies in the context of liver diseases.展开更多
Parkinson’s disease is a common chronic neurodegenerative disease.N-methylation can enhance the neurotoxiicity to dopaminergic neuron in the metabolic process of catechol isoquinolines and Salsolinol N-methyltransfer...Parkinson’s disease is a common chronic neurodegenerative disease.N-methylation can enhance the neurotoxiicity to dopaminergic neuron in the metabolic process of catechol isoquinolines and Salsolinol N-methyltransferases (SNMT) may play an important role in the pathogenesis of PD.A new method including SNMT purification and detecting SNMT activity was developed and displays an excellent sensitivity and stability.In addition,the SNMT activity in Wistar rats substantia nigra,striatum and cerebellum.展开更多
Objective: To understand the function of nicotinamide N-methyltransferase (NNMT) protein as tumor biomarker in renal carcinoma. Methods: Recombinant NNMT protein was used to prepare monoclonal antibodies by hybridoma ...Objective: To understand the function of nicotinamide N-methyltransferase (NNMT) protein as tumor biomarker in renal carcinoma. Methods: Recombinant NNMT protein was used to prepare monoclonal antibodies by hybridoma technique. The diagnostic and prognostic function of NNMT protein in renal carcinoma was evaluated by analyzing 74 renal cancer tissues through immunohistochemical staining for NNMT by using the prepared antibodies. Results: Two hybridomas named 2F8 and 1E7 stably secreting the monoclonal antibodies were isolated successfully, and characters such as isotypes and specificity were determined. NNMT protein was significantly up-regulated in renal cancer and significantly associated with tumor histology and ages. The univariate survival analysis demonstrated that the pT-status, high levels of NNMT, and distant metastasis were significant prognosticators. Conclusion: NNMT is over-expressed in a large proportion in renal cell cancers. High NNMT expression is significantly associated with unfavorable prognosis. However, the prognostic value of NNMT needs further verification in larger sample sizes.展开更多
以氧氯化磷、乙醇胺及1,2-二硬脂酸甘油酯为原料,经环合、磷酰化及水解反应制得1,2-二硬脂酰甘油磷酰乙醇胺(DSPE);在N,N′-羰基二咪唑作用下,DSPE与甲氧基聚乙二醇(mPEG2000)反应合成了1,2-二硬脂酰甘油磷脂酰乙醇胺-N-甲氧基聚乙二醇2...以氧氯化磷、乙醇胺及1,2-二硬脂酸甘油酯为原料,经环合、磷酰化及水解反应制得1,2-二硬脂酰甘油磷酰乙醇胺(DSPE);在N,N′-羰基二咪唑作用下,DSPE与甲氧基聚乙二醇(mPEG2000)反应合成了1,2-二硬脂酰甘油磷脂酰乙醇胺-N-甲氧基聚乙二醇2000(mPEG2000-DSPE),其结构经1 H NMR,IR和MS(ESI)确证。展开更多
Creatine is a naturally occurring derivative of an amino acid commonly utilized in functional foods and pharmaceuticals.Nevertheless,the current industrial synthesis of creatine relies on chemical processes,which may ...Creatine is a naturally occurring derivative of an amino acid commonly utilized in functional foods and pharmaceuticals.Nevertheless,the current industrial synthesis of creatine relies on chemical processes,which may hinder its utilization in certain applications.Therefore,a biological approach was devised that employs whole-cell biocatalysis in the bacterium Corynebacterium glutamicum,which is considered safe for use in food production,to produce safe-for-consumption creatine.The objective of this study was to identify a guanidinoacetate N-methyltransferase(GAMT)with superior catalytic activity for creatine production.Through employing whole-cell biocatalysis,a gamt gene from Mus caroli(Mcgamt)was cloned and expressed in C.glutamicum ATCC 13032,resulting in a creatine titer of 3.37 g/L.Additionally,the study employed a promoter screening strategy that utilized nine native strong promoters in C.glutamicum to enhance the expression level of GAMT.The highest titer was achieved using the P1676 promoter,reaching 4.14 g/L.The conditions of whole-cell biocatalysis were further optimized,resulting in a creatine titer of 5.42 g/L.This is the first report of successful secretory creatine expression in C.glutamicum,which provides a safer and eco-friendly approach for the industrial production of creatine.展开更多
Phosphocholine(PCho)is an intermediate metabolite of nonplastid plant membranes that is essential for salt tolerance.However,how PCho metabolism modulates response to salt stress remains unknown.Here,we characterize t...Phosphocholine(PCho)is an intermediate metabolite of nonplastid plant membranes that is essential for salt tolerance.However,how PCho metabolism modulates response to salt stress remains unknown.Here,we characterize the role of phosphoethanolamine N-methyltransferase 1(PMT1)in salt stress tolerance in Arabidopsis thaliana using a T-DNA insertional mutant,geneediting alleles,and complemented lines.The pmt1 mutants showed a severe inhibition of root elongation when exposed to salt stress,but exogenous ChoCl or lecithin rescued this defect.pmt1 also displayed altered glycerolipid metabolism under salt stress,suggesting that glycerolipids contribute to salt tolerance.Moreover,pmt1 mutants exhibited altered reactive oxygen species(ROS)accumulation and distribution,reduced cell division activity,and disturbed auxin distribution in the primary root compared with wild-type seedlings.We show that PMT1 expression is induced by salt stress and relies on the abscisic acid(ABA)signaling pathway,as this induction was abolished in the aba2-1 and pyl112458 mutants.However,ABA aggravated the salt sensitivity of the pmt1 mutants by perturbing ROS distribution in the root tip.Taken together,we propose that PMT1 is an important phosphoethanolamine N-methyltransferase participating in root development of primary root elongation under salt stress conditions by balancing ROS production and distribution through ABA signaling.展开更多
文摘Choline is a crucial factor in the regulation of sperm membrane structure and fluidity, and this nutrient plays an important role in the maturation and fertilizing capacity of spermatozoa. Transcripts of phosphatidylethanolamine N-methyltransferase (PEMT) and choline dehydrogenase (CHDH), two basic enzymes of choline metabolism, have been observed in the human testis, demonstrating their gene expression in this tissue. In the present study, we explored the contribution of the PEMTand CHDHgene variants to sperm parameters. Two hundred oligospermic and 250 normozoospermic men were recruited. DNA was extracted from the spermatozoa, and the PEMT -774G〉C and CHDH +432G〉T polymorphisms were genotyped. The genotype distribution of the PEMT-774G〉C polymorphism did not differ between oligospermic and normozoospermic men. In contrast, in the case of the CHDH +432G〉T polymorphism, oligospermic men presented the CHDH432GIG genotype more frequently than normozoospermic men (62% vs. 42%, P〈0.001). The PEMT774GIG genotype was associated with a higher sperm concentration compared to the PEMT774GIC and 774C/C genotypes in oligospermic men (12.5±5.6× 10^6 spermatozoa m1-1 vs. 8.3±5.2×10^6 spermatozoa m1-1, P〈0.002) and normozoospermic men (81.5±55.6×10^6 vs. 68.1±44.5×10^6 spermatozoa m1-1, P〈0.006). In addition, the CHDH432G/G genotype was associated with higher sperm concentration compared to CHDH432G.T and 432T/T genotypes in oligospermic (11.8±5.1×10^6 vs. 7.8±5.3×10^6 spermatozoa m1-1, P〈0.003) and normozoospermic men (98.6±62.2×10^6 vs. 58.8±+33.6×10^6 spermatozoa m1-1, P〉0.001). In our series, the PEMT-774G〈C and CHDH +432G〈T polymorphisms were associated with sperm concentration. This finding suggests a possible influence of these genes on sperm quality.
基金Supported by Grants SAF 2003-00967 from Ministerio de Ciencia y Tecnología and FIS 02/0255 from Fondo de Investigación Sanitaria,Instituto de Salud Carlos Ⅲ,Madrid,Spain
文摘AIM: To analyse the role of two common polymorphisms in genes coding for histamine metabolising enzymes as it relates to the risk to develop ulcerative colitis (UC) and the clinical course of these patients. METHODS: A cohort of 229 unrelated patients with UC recruited from a single centre and 261 healthy volunteers were analysed for the presence of Thr105Ile and His645Asp amino acid substitutions at histamine N-methyltransferase (HNMT) and diamine oxidase (ABP1) enzymes, respectively, by amplification-restriction procedures. All patients were phenotyped and followed up for at least 2 years (mean time 11 years). RESULTS: There were no significant differences in the distribution of ABP1 alleles between ulcerative colitis patients and healthy individuals [OR (95% CI) for variant alleles = 1.22 (0.91-1.61)]. However, mutated ABP1 alleles were present with higher frequency among the 58 patients that required immunosuppresive drugs [OR (95 % CI) for carriers of mutated alleles 2.41 (1.21-4.83; P=0.006)], with a significant gene-dose effect (P= 0.0038). In agreement with the predominant role of ABP1 versus HNMT on local histamine metabolism in human bowel, the frequencies for carriers of HNMT genotypes or mutated alleles were similar among patients,regardless clinical evolution, and control individuals. CONCLUSION: The His645Asp polymorphism of the histamine metabolising enzyme ABP1 is related to severity of ulcerative colitis.
基金This work was supported by the National Natural Science Foundation of China(No.31901688).
文摘s Oxidative stress is involved in the progression of neurodegenerative diseases.Previous evidences showed that plasma-logens could improve neurodegenerative diseases.In this study,we investigated the function of phosphoethanolamine plasmalogens enriched with EPA(EPA-pPE)and phosphatidylethanolamine enriched with EPA(EPA-PE)on oxidative damage prevention after hy-drogen peroxide(H2O2)and tert-butylhydroperoxide(t-BHP)challenge in primary hippocampal neurons.Results showed that neurons pretreated with EPA-pPE and EPA-PE demonstrated the ability to alleviate oxidative damage,which was proved by the in-creased cell viability.Moreover,the shape and number of neurons were more similar to those of the control group.Antioxidant acti-vity,apoptosis,as well as TrkB/ERK/CREB signaling pathway were investigated to explore the mechanisms.The results suggested that EPA-PE was superior to EPA-pPE in regulating mitochondrial apoptosis.EPA-pPE was more prominent than EPA-PE in upre-gulating TrkB/ERK/CREB signaling pathway.Phospholipids with EPA exerted neuroprotective effects via inhibiting oxidative stress,suppressing apoptosis,and regulating TrkB/ERK/CREB signaling pathway.Therefore,the results provide a scientific basis for utili-zation of phospholipids enriched with EPA on the treatment of neurodegenerative disease.
文摘Background:Leukemia is a type of cancer that starts in the blood or blood-forming tissues.It results from the clonal proliferation of hematopoietic cells in the bone marrow and/or lymphoid tissues,which subsequently reach the peripheral circulation and can infiltrate other systems.There are many different kinds of leukemia,and treatments are different for each one.Chronic leukemia is with a slower growing than acute leukemia but could be just as life-threatening.Phospholipids are antitumor analogs,such as synthetic phosphoethanolamine,which is a phosphorylated compound capable of controlling cellular proliferation and inducing apoptosis in several types of tumor cells.Methods:K562 and K562-Lucena(MDR+)human chronic myeloid leukemia cells were treated with synthetic phosphoethanolamine(Pho-s).The viability was evaluated by sulforhodamine B(SRB)assay and cell cycle phases,apoptosis,markers expression,and mitochondrial potential were assessed by flow cytometry.Results:Tumor cells formed clusters in suspension and decreased significantly viability.The concentrations for IC50%were obtained.Pho-s treated were 43.1 mM(K562)and 145.9 mM(K562-Lucena MDR+)in a period of 24 hours.Pho-s induced changes in the distribution of cell population phases of cell cycle which showed an increase in fragmented DNA and increased markers expression envolved apoptosis pathways a decrease in the G1/G0 phase.Discussion:Treatment of K562 and K562-Lucena(MDR+)chronic myeloid leukemia cells with Pho-s showed dose and time dependent cytotoxic effects.This cytotoxicity induced a decrease in proliferative capacity,mitochondrial electrical potential,and consequently release of cytochrome C;inhibition of Bcl-2 family protein expression,increase in pro-apoptotic family members Bad and Bax,dependent on p53 expression.Conclusion:This study presented a significant therapeutic potential of Phos-s in this type of leukemia through the apoptotic effects on tumor cells independently of the molecular resistance profile(MDR+).
文摘Synthetic phosphoethanolamine(Pho-s)is a monophosphoester ester with anti-inflammatory and pro-apoptotic properties.Meclizine chloridrate(MC)is a histamine H1 receptor blocker that is also able to inhibit cellular respiration.However,MC does not inhibit cellular respiration in isolated mitochondria such as antimycin and rotenone.Methyl-β-cyclodextrin(MβCD)belongs to theβ-cyclodextrin family,which is capable of removing cholesterol from the plasma membrane.The aim of this study was to evaluate the proliferative effects of meclizine chloridrate and methyl-β-cyclodextrin compounds associated with synthetic phosphoethanolamine in a triple-negative human breast tumor line,MDA-MB-231 Cell viability of the tumor line and normal cells FN1 was evaluated by MTT colorimetric test;the production of free radicals was determined by lipoperoxidation(LPO)test;and the percentage of cell cycle phases and proliferative index was evaluated by flow cytometry.Cell viability demonstrated a significant decrease with the treatments of MβCD,MC and Pho-s associated with MC.The production of free radicals decreases significantly in all treatments.In addition,a significant increase of DNA fragment and decrease in G0/G1 cell cycle phase were observed in cellular percentage with concentrations of 20 and 30 mM of Pho-s in association with MC and MβCD,respectively.
基金supported by grants from the National Natural Science Fund of China(NSFC)(No.82071590).
文摘Cellular metabolism-induced epigenetic regulation is essential for the maintenance of cellular homeostasis.Nicotinamide N-methyltransferase(NNMT)is emerging as a key point of intersection between cellular metabolism and epigenetic regulation and has a central role in various physiological and pathological processes.NNMT catalyzes the methylation of nicotinamide(NAM)using the universal methyl donor S-adenosyl methionine(SAM)to yield S-adeno-syl-L-homocysteine(SAH)and N1-methylnicotinamide(MNAM),directly linking methylation balance with nicotinamide adenosine dinucleotide(NAD+)contents.NNMT acts on either the SAM-methylation balance or both NAD+metabolism,depending on the tissue involved or pathological settings where metabolic demand is increased.Under physiological conditions,the liver act as an essential metabolic organ with abundant NNMT expression,while NNMT hepatic function is not mediated by its methyltransferase activity due to other major methyltransferases such as glycine N-methyltransferase(GNMT)in the liver.However,hepatic NNMT,as well as its metabolite is improperly regulated and linked to the worse pathological states in liver diseases,including alcoholic liver disease,non-alcoholic fatty liver disease(NAFLD),liver cirrhosis,and hepatocellular carcinoma(HCC),suggesting a potential role in the process of liver diseases.In this review,we summarize how NNMT regulates cell methylation balance and NAD metabolism,and extensively outline the current knowledge concerning the functions of NNMT in hepatic metabolism including glucose,lipid and energy,with a specific focus on the contribution of NNMT to the pathophysiology of liver-related diseases.NNMT is involved in the development and progression of liver diseases.Understanding the complex NNMT regulatory network and its effects on pathogenesis could provide new therapeutic strategies in the context of liver diseases.
文摘Parkinson’s disease is a common chronic neurodegenerative disease.N-methylation can enhance the neurotoxiicity to dopaminergic neuron in the metabolic process of catechol isoquinolines and Salsolinol N-methyltransferases (SNMT) may play an important role in the pathogenesis of PD.A new method including SNMT purification and detecting SNMT activity was developed and displays an excellent sensitivity and stability.In addition,the SNMT activity in Wistar rats substantia nigra,striatum and cerebellum.
基金Project supported by the Science Foundation of Health Bureau of Zhejiang Province (Nos. 2005A055 and 2008B114)the Science Foundation of Education Bureau of Zhejiang Province (No. 20061271), China
文摘Objective: To understand the function of nicotinamide N-methyltransferase (NNMT) protein as tumor biomarker in renal carcinoma. Methods: Recombinant NNMT protein was used to prepare monoclonal antibodies by hybridoma technique. The diagnostic and prognostic function of NNMT protein in renal carcinoma was evaluated by analyzing 74 renal cancer tissues through immunohistochemical staining for NNMT by using the prepared antibodies. Results: Two hybridomas named 2F8 and 1E7 stably secreting the monoclonal antibodies were isolated successfully, and characters such as isotypes and specificity were determined. NNMT protein was significantly up-regulated in renal cancer and significantly associated with tumor histology and ages. The univariate survival analysis demonstrated that the pT-status, high levels of NNMT, and distant metastasis were significant prognosticators. Conclusion: NNMT is over-expressed in a large proportion in renal cell cancers. High NNMT expression is significantly associated with unfavorable prognosis. However, the prognostic value of NNMT needs further verification in larger sample sizes.
文摘以氧氯化磷、乙醇胺及1,2-二硬脂酸甘油酯为原料,经环合、磷酰化及水解反应制得1,2-二硬脂酰甘油磷酰乙醇胺(DSPE);在N,N′-羰基二咪唑作用下,DSPE与甲氧基聚乙二醇(mPEG2000)反应合成了1,2-二硬脂酰甘油磷脂酰乙醇胺-N-甲氧基聚乙二醇2000(mPEG2000-DSPE),其结构经1 H NMR,IR和MS(ESI)确证。
基金funded by National Natural Science Foundation of China(no.32272279)the Key R&D project of Qingdao Science and Technology Plan(22-3-3-hygg-29-hy).
文摘Creatine is a naturally occurring derivative of an amino acid commonly utilized in functional foods and pharmaceuticals.Nevertheless,the current industrial synthesis of creatine relies on chemical processes,which may hinder its utilization in certain applications.Therefore,a biological approach was devised that employs whole-cell biocatalysis in the bacterium Corynebacterium glutamicum,which is considered safe for use in food production,to produce safe-for-consumption creatine.The objective of this study was to identify a guanidinoacetate N-methyltransferase(GAMT)with superior catalytic activity for creatine production.Through employing whole-cell biocatalysis,a gamt gene from Mus caroli(Mcgamt)was cloned and expressed in C.glutamicum ATCC 13032,resulting in a creatine titer of 3.37 g/L.Additionally,the study employed a promoter screening strategy that utilized nine native strong promoters in C.glutamicum to enhance the expression level of GAMT.The highest titer was achieved using the P1676 promoter,reaching 4.14 g/L.The conditions of whole-cell biocatalysis were further optimized,resulting in a creatine titer of 5.42 g/L.This is the first report of successful secretory creatine expression in C.glutamicum,which provides a safer and eco-friendly approach for the industrial production of creatine.
基金supported by the National Key Research and Development Program of China(Grant No.2016YFD0100704)Key R&D Program of Zhejiang(2022C02030)。
文摘Phosphocholine(PCho)is an intermediate metabolite of nonplastid plant membranes that is essential for salt tolerance.However,how PCho metabolism modulates response to salt stress remains unknown.Here,we characterize the role of phosphoethanolamine N-methyltransferase 1(PMT1)in salt stress tolerance in Arabidopsis thaliana using a T-DNA insertional mutant,geneediting alleles,and complemented lines.The pmt1 mutants showed a severe inhibition of root elongation when exposed to salt stress,but exogenous ChoCl or lecithin rescued this defect.pmt1 also displayed altered glycerolipid metabolism under salt stress,suggesting that glycerolipids contribute to salt tolerance.Moreover,pmt1 mutants exhibited altered reactive oxygen species(ROS)accumulation and distribution,reduced cell division activity,and disturbed auxin distribution in the primary root compared with wild-type seedlings.We show that PMT1 expression is induced by salt stress and relies on the abscisic acid(ABA)signaling pathway,as this induction was abolished in the aba2-1 and pyl112458 mutants.However,ABA aggravated the salt sensitivity of the pmt1 mutants by perturbing ROS distribution in the root tip.Taken together,we propose that PMT1 is an important phosphoethanolamine N-methyltransferase participating in root development of primary root elongation under salt stress conditions by balancing ROS production and distribution through ABA signaling.