Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy ...Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood.Methods:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical correlations.We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival curves.Additionally,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and ubiquitination.Drug sensitivity analysis was performed to assess the relationship between POLY expression and drug response.Results:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer types.Some POLYs showed heightened expression in specific cancer subtypes,while others exhibited low expression.Kaplan-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and ACC.Cox analysis further validated these findings.Alteration patterns of POLYs varied significantly among different cancer types and were associated with poorer survival outcomes.Significant correlations were observed between the expression of POLY members and immune cells,DDR pathways,and ubiquitination.Drug sensitivity analysis indicated an inverse relationship between POLY expression and drug response.Conclusion:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and immunological biomarkers for various cancer types.Additionally,targeting POLYs therapeutically holds promise for tumor immunotherapy.展开更多
Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been w...Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially per- oxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly（ADP-ribose） polymerase （PARP） upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neu- ronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the in- volvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.展开更多
The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress ...The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress induced robust DNA damage and wide spread inflamma- tory responses are common pathologies of various CNS diseases, the attention towards PARP-1 as a therapeutic target has been amplifying. This review highlights the multiple roles of PARP- 1 in neurological diseases and po- tential of PARP- 1 inhibitors to enter clinical translation.展开更多
Poly （ADP-ribose） polymerase-1 （PARP-1） can exacerbate ischemic brain injury and lessen ischemic neuronal death, which may be associated with PARP-1 polymorphisms. The present study investigated human PARP-1 gene ...Poly （ADP-ribose） polymerase-1 （PARP-1） can exacerbate ischemic brain injury and lessen ischemic neuronal death, which may be associated with PARP-1 polymorphisms. The present study investigated human PARP-1 gene polymorphisms in various Chinese nationalities, the results of which could potentially help in the treatment and prevention of neurologic diseases. Genetic polymorphisms of seven exons in the PARP-1 gene, in 898 Chinese Han, Buyi, Shui, Miao, and Zhuang subjects, were investigated by PCR-single-strand conformation polymorphism. A single-strand conformation polymorphism variant in exons 12, 13, 16, and 17 of the PARP-1 gene was identified in 148 people, with two stationary bands showing three degenerative single strands. Results showed that the PARP-1 gene polymorphisms exist in various nationalities, and may act as a biomarker for susceptibility to disease.展开更多
The use of chemotherapeutic regimens for the treatment of pancreatic cancer is still limited because pancreatic cancer is usually diagnosed at an advanced stage as a refractory disease in which symptoms are difficult ...The use of chemotherapeutic regimens for the treatment of pancreatic cancer is still limited because pancreatic cancer is usually diagnosed at an advanced stage as a refractory disease in which symptoms are difficult to recognize in the early stages.Furthermore,at advanced stages,there are important challenges to achieve clinical benefit and symptom resolution,even with the use of an expanded spectrum of anticancer drugs.Recently,a point of reduced susceptibility to conventional chemotherapies by breast cancer susceptibility gene(BRCA)mutations led to a new perspective for overcoming the resistance of pancreatic cancer within the framework of increased genome instability.Poly(ADP-Ribose)polymerase(PARP)-1 is an enzyme that can regulate intrinsic functions,such as response to DNA damage.Therefore,in an environment where germline mutations in BRCAs(BRCAness)inhibit homologous recombination in DNA damage,resulting in a lack of DNA damage response,a key role of PARP-1 for the adaptation of the genome instability could be further emphasized.Here,we summarized the key functional role of PARP-1 in genomic instability of pancreatic cancer with the BRCAness phenotype and listed clinical applications and outcomes of PARP-1 inhibitors to highlight the importance of targeting PARP-1 activity.展开更多
Objective:To investigate the polyadenylation of mRNA in E. Coli. Methods: The mRNA of E. Coli was enriched from the total RNA with oligo(dT)-cellulose, prior to reverse transcription using oligo(dT)18as the primer. Do...Objective:To investigate the polyadenylation of mRNA in E. Coli. Methods: The mRNA of E. Coli was enriched from the total RNA with oligo(dT)-cellulose, prior to reverse transcription using oligo(dT)18as the primer. Double-stranded cDNA was subsequently synthesized, which was subjected to digestion with Sau3A I to produce multiple gene fragments for ligation with the adapters. PCR was carried out in 10 groups according to 10 different pairs of the selective primers, and the PCR products were then cloned into T-vectors. Results: More than 100 gene fragments had been cloned, 30 of which were sequenced. Conclusion:Polyadenylation of E. Coli mRNA may not be a biochemical curiosity but a general attribute of bacterial mRNA.展开更多
Background Poly（ADP-ribose） polymerase （PARP） plays an important role in the death of retinal capillary cells in diabetic retinopathy （DR） partly via its regulation of nuclear factor kappa B （NF-κB）. The curr...Background Poly（ADP-ribose） polymerase （PARP） plays an important role in the death of retinal capillary cells in diabetic retinopathy （DR） partly via its regulation of nuclear factor kappa B （NF-κB）. The current study investigated the effect of the regimen of Gaoshan Hongjingtian （RG） on the mechanism of PARP regulation of NF-κB, and demonstrated the possible impact of the RG and Gaoshan Hongjingtian （Rhodiola sachalinensis, RS） on diabetic retinopathy. Methods Wistar rats were made diabetic by administering streptozotocin. They were then assigned to three groups at random. After 2 months, the three groups of these diabetic rats were treated with RS or RG, or untreated. Analyses of expression levels of PARP, NF-κB, and intercellular adhesion molecule-1 （ICAM-1） in the retinas of rats in different groups were performed by Western blotting and immunohistochemical assays, and mRNA levels of NF-κB and ICAM-1 were determined by real-time polymerase chain reaction （PCR）. In addition, the basement membranes of capillaries in the rats＇ retinas were observed using electron microscopy, and diabetes-induced capillary degeneration （ghost pericytes and acellular capillaries） were quantitated. Results From the third month after the injection of streptozotocin, the diabetic rats were given daily RG, RS or tap water separately. The diabetic rats failed to gain weight compared with normal age-matched rats, whereas their glycated hemoglobin levels were significantly increased. After 5 months, the mRNA levels of NF-KB and ICAM-1 and the protein expression of PARP, NF-κB, and ICAM-1 were significantly increased in the retinas of diabetic rats in the untreated group compared with the nondiabetic controls. After 8 months, the number of degenerated retinal capillaries （ghost pericytes and acellular capillaries） was significantly increased in the diabetic rats in the untreated group compared with normal age-matched rats. RG and RS inhibited diabetes-induced over-expression of PARP, NF-KB, and ICAM-1 in the retinas of diabetic rats at the end of 5-month diabetic duration. Treatment using RG and RS significantly inhibited increases in the number of acellular capillaries and pericyte ghosts and suppressed the basement membrane thickening in the retinas of rats with diabetes for 8 months compared with the control diabetic rats. Conclusions These results indicate that PARP plays an important role in the pathogenesis of diabetic retinopathy. RS and RG may have acted on the mechanism of PARP regulation of NF-κB, which suppressed the expression of NF-KB and ICAM-1, and led to the inhibition of retinal capillary degeneration.展开更多
A new method has been developed to assay poly(ADP-ribose) polymerase (PARP) activity in plant tissues through determining the content of nicotinamide (NIC) produced by enzymatic reaction by linear sweeping polarograph...A new method has been developed to assay poly(ADP-ribose) polymerase (PARP) activity in plant tissues through determining the content of nicotinamide (NIC) produced by enzymatic reaction by linear sweeping polarographic method. The detection limit of NIC was 0.03μmol/L, the calibration graph was linear up to 5μmol/L ( r = 0.999). The recoveries were approximately in the range of 92% to 98% and the relative standard deviations were less展开更多
Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoqu...Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoquinolinone （DPQ）, a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms. Methods Studies were performed with I/R rats＇ hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB （NF-KB）, intercellular adhesion molecule-1 （ICAM-1）, cyclooxygenase-2 （COX-2） and matrix metalloproteinase-9 （MMP-9） were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-313 （GSK- 3β） and forkhead transcription factor FOXO3a. Results Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from （35±5）% to （20±4）% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-KB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a. Conclusion The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly （ADP-ribose） polymerase reduced heart I/R injury in rats.展开更多
The aim of this paper is to study the changes of apoptosis and cell cycle progression in HeLa cells after the poly(ADP-ribose)polymerase(PARP)was inhibited by its inhibitor 3-aminobenzamide(3-AB)and the mechan-isms of...The aim of this paper is to study the changes of apoptosis and cell cycle progression in HeLa cells after the poly(ADP-ribose)polymerase(PARP)was inhibited by its inhibitor 3-aminobenzamide(3-AB)and the mechan-isms of PARP action on HeLa cells damaged by irra-diation.Flow cytometry(FCM)was used to examine the PARP expression and the percentage of apoptotic cells and cell cycle progression.The percentage of HeLa cells with positive expression of PARP protein 2,4,8 and 12 h after administrated with 3-AB was significantly lower than that of the control(P<0.01).The percentages of apoptotic cells in the 3-AB plus irradiation group at the time points of 2,8,12 and 24 h after 2 Gy irradiation were higher than that in the irradiation group(P<0.01 or P<0.05)and the percentage of G2 cells decreased signifi-cantly(P<0.01 or P<0.05).It indicates that 3-AB can rapidly inhibit PARP expression of HeLa cells,promote cell apoptosis and block G2 arrest induced by irradiation.展开更多
Background Severe sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients.This study aimed to investigate the association of poly（ADP-ribose） polymerase-1 （PARP-1） activi...Background Severe sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients.This study aimed to investigate the association of poly（ADP-ribose） polymerase-1 （PARP-1） activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock.Methods A total of 64 patients with septic shock were divided into the survival group （n=41） and the nonsurvival group （n=23） according to mortality at 28 days after enrollments.PARP-1 activity in circulating mononuclear cells,brain natriuretic peptide,Acute Physiology and Chronic Health Evaluation Ⅱ score,the cardiac index （CI）,the cardiac function index （CFI）,global ejection fraction （GEF）,and the left ventricular contractility index （dp/dt max） were measured after admission to the intensive care unit.Results PARP-1 activity in circulating mononuclear cells of nonsurvival patients with septic shock was significantly higher than that in survival patients.PARP-1 activity in circulating mononuclear cells was strongly,negatively correlated with the CI,the CFI,GEE and dp/dt max.Multiple Logistic regression analysis showed that PARP-1 activity in circulating mononuclear cells was an independent risk factor of myocardial dysfunction.The optimal cutoff point of PARP-1 activity for predicting 28-day mortality was 942 nmol/L with a sensibility of 78.2% and specificity of 65.1%.Conclusion PARP-1 activity in circulating mononuclear cells is significantly associated with myocardial dysfunction and may have prognostic value in patients with septic shock.展开更多
BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)...BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer cells.AIM To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.METHODS Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the study.Calcium influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence staining.Changes in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay kits.AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.RESULTS Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells.Then,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were observed.In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.CONCLUSION This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.展开更多
基金supported by the project of funds by the Consultation of Provincial Department and University for S&T Innovation granted by Hebei Provincial Department of Science and Technology and Hebei Medical University(2020TXZH04).
文摘Introduction:DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis.However,the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood.Methods:We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases(POLYs)and their clinical correlations.We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time(OS)using Kaplan-Meier survival curves.Additionally,we investigated the correlations between POLY expression and immune cells,DNA damage repair(DDR)pathways,and ubiquitination.Drug sensitivity analysis was performed to assess the relationship between POLY expression and drug response.Results:Our analysis revealed that 14 out of 15 POLYs exhibited significantly distinct expression patterns between tumor and normal samples across most cancer types,except for DNA nucleotidylexotransferase(DNTT).Specifically,POLD1 and POLE showed elevated expression in almost all cancers,while POLQ exhibited high expression levels in all cancer types.Some POLYs showed heightened expression in specific cancer subtypes,while others exhibited low expression.Kaplan-Meier survival curves demonstrated significant prognostic value of POLYs in multiple cancers,including PAAD,KIRC,and ACC.Cox analysis further validated these findings.Alteration patterns of POLYs varied significantly among different cancer types and were associated with poorer survival outcomes.Significant correlations were observed between the expression of POLY members and immune cells,DDR pathways,and ubiquitination.Drug sensitivity analysis indicated an inverse relationship between POLY expression and drug response.Conclusion:Our comprehensive study highlights the significant role of POLYs in cancer development and identifies them as promising prognostic and immunological biomarkers for various cancer types.Additionally,targeting POLYs therapeutically holds promise for tumor immunotherapy.
基金Department of Biotechnology Govt of India,for their financial support to Dr.Ashutosh Kumar via grant BT/527/NE/TBP/2013the financial support from Department of Pharmaceuticals,Ministry of Chemical and Fertilizers and NIPER Hyderabad for their support
文摘Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that jimit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially per- oxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly（ADP-ribose） polymerase （PARP） upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neu- ronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the in- volvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.
文摘The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress induced robust DNA damage and wide spread inflamma- tory responses are common pathologies of various CNS diseases, the attention towards PARP-1 as a therapeutic target has been amplifying. This review highlights the multiple roles of PARP- 1 in neurological diseases and po- tential of PARP- 1 inhibitors to enter clinical translation.
基金the National Natural Science Foundation of China, No. 30972500the Natural Science Foundation of Guangdong Province, No. 7301507
文摘Poly （ADP-ribose） polymerase-1 （PARP-1） can exacerbate ischemic brain injury and lessen ischemic neuronal death, which may be associated with PARP-1 polymorphisms. The present study investigated human PARP-1 gene polymorphisms in various Chinese nationalities, the results of which could potentially help in the treatment and prevention of neurologic diseases. Genetic polymorphisms of seven exons in the PARP-1 gene, in 898 Chinese Han, Buyi, Shui, Miao, and Zhuang subjects, were investigated by PCR-single-strand conformation polymorphism. A single-strand conformation polymorphism variant in exons 12, 13, 16, and 17 of the PARP-1 gene was identified in 148 people, with two stationary bands showing three degenerative single strands. Results showed that the PARP-1 gene polymorphisms exist in various nationalities, and may act as a biomarker for susceptibility to disease.
文摘The use of chemotherapeutic regimens for the treatment of pancreatic cancer is still limited because pancreatic cancer is usually diagnosed at an advanced stage as a refractory disease in which symptoms are difficult to recognize in the early stages.Furthermore,at advanced stages,there are important challenges to achieve clinical benefit and symptom resolution,even with the use of an expanded spectrum of anticancer drugs.Recently,a point of reduced susceptibility to conventional chemotherapies by breast cancer susceptibility gene(BRCA)mutations led to a new perspective for overcoming the resistance of pancreatic cancer within the framework of increased genome instability.Poly(ADP-Ribose)polymerase(PARP)-1 is an enzyme that can regulate intrinsic functions,such as response to DNA damage.Therefore,in an environment where germline mutations in BRCAs(BRCAness)inhibit homologous recombination in DNA damage,resulting in a lack of DNA damage response,a key role of PARP-1 for the adaptation of the genome instability could be further emphasized.Here,we summarized the key functional role of PARP-1 in genomic instability of pancreatic cancer with the BRCAness phenotype and listed clinical applications and outcomes of PARP-1 inhibitors to highlight the importance of targeting PARP-1 activity.
基金This work was partly supported by research grants No. 81072703 （to Dr. Yu） from the National Natural Science Foundation, Beijing, P.R. China, a research grant No. 10411951700 （to Dr. Zhang） from Science and Technology Commission of Shanghai Municipality, Shanghai, P.R. China.The authors confirm that there are no conflicts of interests.
文摘Objective:To investigate the polyadenylation of mRNA in E. Coli. Methods: The mRNA of E. Coli was enriched from the total RNA with oligo(dT)-cellulose, prior to reverse transcription using oligo(dT)18as the primer. Double-stranded cDNA was subsequently synthesized, which was subjected to digestion with Sau3A I to produce multiple gene fragments for ligation with the adapters. PCR was carried out in 10 groups according to 10 different pairs of the selective primers, and the PCR products were then cloned into T-vectors. Results: More than 100 gene fragments had been cloned, 30 of which were sequenced. Conclusion:Polyadenylation of E. Coli mRNA may not be a biochemical curiosity but a general attribute of bacterial mRNA.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 81072844）.
文摘Background Poly（ADP-ribose） polymerase （PARP） plays an important role in the death of retinal capillary cells in diabetic retinopathy （DR） partly via its regulation of nuclear factor kappa B （NF-κB）. The current study investigated the effect of the regimen of Gaoshan Hongjingtian （RG） on the mechanism of PARP regulation of NF-κB, and demonstrated the possible impact of the RG and Gaoshan Hongjingtian （Rhodiola sachalinensis, RS） on diabetic retinopathy. Methods Wistar rats were made diabetic by administering streptozotocin. They were then assigned to three groups at random. After 2 months, the three groups of these diabetic rats were treated with RS or RG, or untreated. Analyses of expression levels of PARP, NF-κB, and intercellular adhesion molecule-1 （ICAM-1） in the retinas of rats in different groups were performed by Western blotting and immunohistochemical assays, and mRNA levels of NF-κB and ICAM-1 were determined by real-time polymerase chain reaction （PCR）. In addition, the basement membranes of capillaries in the rats＇ retinas were observed using electron microscopy, and diabetes-induced capillary degeneration （ghost pericytes and acellular capillaries） were quantitated. Results From the third month after the injection of streptozotocin, the diabetic rats were given daily RG, RS or tap water separately. The diabetic rats failed to gain weight compared with normal age-matched rats, whereas their glycated hemoglobin levels were significantly increased. After 5 months, the mRNA levels of NF-KB and ICAM-1 and the protein expression of PARP, NF-κB, and ICAM-1 were significantly increased in the retinas of diabetic rats in the untreated group compared with the nondiabetic controls. After 8 months, the number of degenerated retinal capillaries （ghost pericytes and acellular capillaries） was significantly increased in the diabetic rats in the untreated group compared with normal age-matched rats. RG and RS inhibited diabetes-induced over-expression of PARP, NF-KB, and ICAM-1 in the retinas of diabetic rats at the end of 5-month diabetic duration. Treatment using RG and RS significantly inhibited increases in the number of acellular capillaries and pericyte ghosts and suppressed the basement membrane thickening in the retinas of rats with diabetes for 8 months compared with the control diabetic rats. Conclusions These results indicate that PARP plays an important role in the pathogenesis of diabetic retinopathy. RS and RG may have acted on the mechanism of PARP regulation of NF-κB, which suppressed the expression of NF-KB and ICAM-1, and led to the inhibition of retinal capillary degeneration.
文摘A new method has been developed to assay poly(ADP-ribose) polymerase (PARP) activity in plant tissues through determining the content of nicotinamide (NIC) produced by enzymatic reaction by linear sweeping polarographic method. The detection limit of NIC was 0.03μmol/L, the calibration graph was linear up to 5μmol/L ( r = 0.999). The recoveries were approximately in the range of 92% to 98% and the relative standard deviations were less
基金This study was supported by grants from the Natural Science Foundation of Shandong Province, China （No.ZR2010HM069） and the Technology Development Projects of Taian City （No. 20093077）.
文摘Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoquinolinone （DPQ）, a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms. Methods Studies were performed with I/R rats＇ hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB （NF-KB）, intercellular adhesion molecule-1 （ICAM-1）, cyclooxygenase-2 （COX-2） and matrix metalloproteinase-9 （MMP-9） were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-313 （GSK- 3β） and forkhead transcription factor FOXO3a. Results Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from （35±5）% to （20±4）% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-KB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a. Conclusion The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly （ADP-ribose） polymerase reduced heart I/R injury in rats.
基金supported by the National Natural Science Foundation of China(Grant No.30570546).
文摘The aim of this paper is to study the changes of apoptosis and cell cycle progression in HeLa cells after the poly(ADP-ribose)polymerase(PARP)was inhibited by its inhibitor 3-aminobenzamide(3-AB)and the mechan-isms of PARP action on HeLa cells damaged by irra-diation.Flow cytometry(FCM)was used to examine the PARP expression and the percentage of apoptotic cells and cell cycle progression.The percentage of HeLa cells with positive expression of PARP protein 2,4,8 and 12 h after administrated with 3-AB was significantly lower than that of the control(P<0.01).The percentages of apoptotic cells in the 3-AB plus irradiation group at the time points of 2,8,12 and 24 h after 2 Gy irradiation were higher than that in the irradiation group(P<0.01 or P<0.05)and the percentage of G2 cells decreased signifi-cantly(P<0.01 or P<0.05).It indicates that 3-AB can rapidly inhibit PARP expression of HeLa cells,promote cell apoptosis and block G2 arrest induced by irradiation.
基金This study was supported by the grants from the National Natural Science Foundation of China （No. 81171784） and Zhejiang Province Natural Science Fotmdation （No. Z2100237 and No. Y2110801）.
文摘Background Severe sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients.This study aimed to investigate the association of poly（ADP-ribose） polymerase-1 （PARP-1） activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock.Methods A total of 64 patients with septic shock were divided into the survival group （n=41） and the nonsurvival group （n=23） according to mortality at 28 days after enrollments.PARP-1 activity in circulating mononuclear cells,brain natriuretic peptide,Acute Physiology and Chronic Health Evaluation Ⅱ score,the cardiac index （CI）,the cardiac function index （CFI）,global ejection fraction （GEF）,and the left ventricular contractility index （dp/dt max） were measured after admission to the intensive care unit.Results PARP-1 activity in circulating mononuclear cells of nonsurvival patients with septic shock was significantly higher than that in survival patients.PARP-1 activity in circulating mononuclear cells was strongly,negatively correlated with the CI,the CFI,GEE and dp/dt max.Multiple Logistic regression analysis showed that PARP-1 activity in circulating mononuclear cells was an independent risk factor of myocardial dysfunction.The optimal cutoff point of PARP-1 activity for predicting 28-day mortality was 942 nmol/L with a sensibility of 78.2% and specificity of 65.1%.Conclusion PARP-1 activity in circulating mononuclear cells is significantly associated with myocardial dysfunction and may have prognostic value in patients with septic shock.
文摘BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer cells.AIM To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.METHODS Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the study.Calcium influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence staining.Changes in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay kits.AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.RESULTS Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells.Then,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were observed.In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.CONCLUSION This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.
