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Pharmacophore-based structure optimization of angiotensin converting enzyme inhibitory peptide

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Science China Chemistry 2008年第8期51卷 786-793页

作者： WANG Wei SHEN ShengRong FENG FengQin Department of Food Science and Nutrition Zhejiang University Hangzhou 310029 China

Chemical feature based pharmacophore models were generated for an angiotensin converting enzyme(ACE) inhibitory peptide using the Discovery Studio 2.0 pharmacophore modeling approach. The pharmacophore hypothesis selected has five features(one negative ionizable region,one hydrogen bond donor,one hydrogen bond acceptor and two hydrophobic functional groups). Additionally,ACE inhibitory hexapeptide previously obtained from silkworm pupae protein was optimized to target the ACE based on the selected pharmacophore. The results suggest that tri-peptide(thr-val-phe) may be structural determinant of ACE activity. Docking studies further provided confidence for the validity of the selected pharmacophore model to perform structure optimization of the ACE inhibitory peptide.

关键词： angiotensin converting enzyme inhibitory peptide pharmacophore model docking

Demethylation of tumor necrosis factor-α converting enzyme promoter associated with high hepatitis B e antigen level in chronic hepatitis B

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World Journal of Gastroenterology 2015年第27期21卷 8382-8388页

作者： Zhen-Li Wang Shuai Gao Xin-You Li Feng-Kai Sun Feng Li Yu-Chen Fan Kai Wang Department of Hepatology Qilu Hospital of Shandong University Institute of Hepatology Shandong University

AIM: To evaluate tumor necrosis factor-α converting enzyme(TACE) methylation status in patients with chronic hepatitis B(CHB).METHODS: Eighty patients with hepatitis B e antigen(HBe Ag)-positive CHB, 80 with HBe Ag-negative CHB, and 40 healthy controls(HCs) were randomly enrolled in this study. Genomic DNA was extracted from peripheral blood mononuclear cells and methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The clinical and laboratory parameters were ***: One hundred and thirty of 160 patients with CHB(81.25%) and 38 of 40 HCs(95%) displayed TACE promoter methylation. The difference was significant(χ2 = 4.501, P 0.05). In the HBe Ag-positive group, TACE methylation frequency was significantly negatively correlated with HBe Ag(r =-0.602, P < 0.01), alanine aminotransferase(r =-0.461, P < 0.01) and aspartate aminotransferase(r =-0.329, P < 0.01). CONCLUSION: Patients with HBe Ag-positive CHB have aberrant demethylation of the TACE promoter, which may potentially serve as a biomarker for HBe Ag seroconversion.

关键词： Tumor necrosis factor-α converting enzyme Methylation Chronic hepatitis B Methylation-specificpolymerase chain reaction Biomarker

Correlation of angiotensin converting enzyme gene polymorphism with perioperative myocardial protection under extracorporeal circulation

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Asian Pacific Journal of Tropical Medicine 2012年第12期5卷 995-999页

作者： Wei Yang Xiao Dong Bin Li Xiao-Qiang Zhang Yuan Zeng Yi-Ping Wei Jian-Liang Zhou Yan-Hua Tang Jian-Jun Xu Department of Cardiothoracic Surgery Second Affiliated Hospital to Nanchang University

Objective:To observe the expression of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),cardiac troponin 详细信息

Objective:To observe the expression of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),cardiac troponin converting enzyme genes and myocardial ***:Sixty-three patients suffered from rheumatic mitral stenosis and scheduled for mitral valve replacement with CPB, were randomly divided into three groups according polymorphisms in angiotensin converting enzyme genes:typeⅡ,type ID,type DD(each=21).Blood samples were withdrawn from artery before operation(T1),at the beginning of CPB(T2),30 min after CPB(T3),(T4) at the end of CPB(T5), 2 h after CPB(T6),6 h after CPB(17) to measure the expression of ACE,AngⅡ,cTnⅠ,CK-MB, ***:The level of ACE during and after CPB were significantly higher than those before CPB(P<0.05).As extension of CPB time,the expression of ACE was *** level of cTnⅠ, CK-MB,Myo after CPB were significantly higher than those before CPB(P<0.05).The level of cTnⅠ,CK-MB and Myo were highest at T7,T6 and T5 and T7,*** level of ACE,AngⅡ,cTnⅠin patients with DD genotype was significantly higher than the ID andⅡgenotype(P< 0.05).Besides,the level of ACE,AngⅡin patients with ID genotype was significantly higher than the II(P< 0.05).Conclusions:There is certain correlation between CPB perioperative midterm ACE and cTnⅠ,Myo,*** DD genotype is a susceptibility gene of the CPB perioperative myocardial injury.

关键词： Angiotensin converting enzyme ACE gene polymorphism Cardiopulmonary bypass perioperative Myocardial injury Myocardial markers

Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis

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World Journal of Gastroenterology 2017年第48期23卷 8439-8442页

作者： Aline Silva Miranda Ana Cristina Sim?es e Silva In-terdisciplinary Laboratory of Medical Investigation Faculty of MedicineFederal University of Minas Gerais Laboratory of Neurobiology Department of MorphologyInstitute of Biological SciencesFederal University of Minas Gerais Department of Pediatrics Faculty of MedicineFederal University of Minas Gerais

The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.

关键词： Renin angiotensin system Angiotensin converting enzyme Angiotensin Ⅱ Angiotensin-(1-7) Chronic hepatitis B hepatic cirrhosis Liver fibrosis

Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome

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The Journal of Biomedical Research 2019年第3期33卷 201-207页

作者： Aravind Selvin Kumar Ramanathan Balakrishnan Karuppiah Murali Vijayan Kamaraj Raju Dhivakar Mani Rathika Chinniah Manikandan Thirunavukkarasu Padma Malini Ravi Jeyaram Illiayaraja Krishnan Prabha Senguttuvan Department of Pediatric Nephrology Institute of Child Health and Hospital for Children Department of Medical Genetics The Tamil Nadu Dr.M.G.R.Medical University Department of Immunology School of Biological SciencesMadurai Kamaraj University Department of Biotechnology and Genetic Engineering Bharathidasan University Department of Clinical Research Narayana Health City Department of Pediatric Nephrology Dr.Mehta’s Children’s Hospital

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%-15% of nephrotic syndrome cases are non-responders of steroid treatment(SRNS).Angiotensin converting enzyme(ACE)(I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE(I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome(162 boys and 98 girls) and 218(140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE(I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases(minimal change disease, n = 51;focal segmental glomerulosclerosis, n = 27;diffuse mesangial proliferation, n = 8). We segregated them into the minimal change disease/focal segmental glomerulosclerosis groups and observed that the ACE’D’ allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the ’Ⅰ’ allele was assessed as having very weak association in cases of minimal change disease. ’Ⅱ’ genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of’ID’ genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE(I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.

关键词： angiotensin converting enzyme focal segmental glomerulosclerosis minimal change disease nephrotic syndrome

Protective effect of the angiotensin-converting enzyme inhibitor perindopril on diabetic glomerulopathy in streptozotocin-induced diabetic rats

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Chinese Medical Journal 1998年第4期 19-21页

作者：严励杨荣泽程桦傅祖植钟光恕严棠

Objectives To evaluate the protective effect of the angiotensin converting enzyme inhibitor perindopril on diabetic glomerulopathy in rats with experimentally induced diabetes and explore its possible mechanisms. Methods Ninety two adult male Wistar rats were randomly allocated into diabetes mellitus (DM), diabetes mellitus + perindopril (DMP) and control (C) groups. According to the duration of diabetes or observation (1, 3, 6 months), each group was randomly subdivided into DM1, DM3, DM6; DMP1, DMP3, DMP6; and C1, C3, C6 groups. Diabetes was induced by intraperitoneal injection of streptozotocin. The rats in the DMP groups received perindopril 1 mg·kg 1 ·d 1 , through gastric intubation. Urinary protein excretion rate was determined by the method of Coomassie brilliant blue. Plasma renin activity, renal tissue renin activity, and plasma and renal tissue angiotensin Ⅱ concentration were assayed by radioimmunoassay (RIA). Renal tissue total RNA was extracted by the Chomezymskis AGPC method. Renal angiotensinogen mRNA expression level was assessed by slot blot hybridization using a full length rat angiotensinogen cDNA probe labelled with 32 P dCTP and a random primer. Results There was increased activity of the renin angiotensin system in diabetic rats. Perindopril decreased proteinuria and delayed the progression of glomerular basement membrane thickening. However, it did not reduce the expansion of the mesangial matrix (P<0.05). Renin activity increased and angiotensin Ⅱ concentration decreased significantly in both plasma and renal tissue in diabetes+perindopril groups (P<0.05). Conclusions Perindopril may help prevent the progression of diabetic glomerulopathy, and the inhibition of renin angiotensin system activity may be a mechanism for this action.

关键词： streptozotocin converting 傅祖植严棠

Expression of interleukin 1β converting enzyme in 5-FU induced apoptosis in esophageal carcinoma cells

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World Journal of Gastroenterology 1999年第1期5卷 55-57页

作者： DENG Li Ying 1, ZHANG Yun Han 2, XU Ping 2, YANG Su Min 1 and YUAN Xue Bin 1

AIM To study the role of interleukin 1β converting enzyme (ICE) in antitumor drug induced apoptosis in tumor cells. METHODS Morphological changes in human esophageal carcinoma Eca 109 cells after treated with 5 fluorouracil (5 FU) were observed under light and electron microscope. Expression of ICE in the tumor cells exposed to 5 FU was examined by the immunocytochemical method. RESULTS The cells treated with 5 FU displayed disappearance of nucleoli, chromatin gathering under nuclear envelope, karyorrhexis, budding and the formation of apoptotic bodies. The expression of ICE was negative in control cells, and 5 FU could induce the ICE expression in Eca 109 cells undergoing apoptosis. The number and the staining intensity of positive cells increased with the extension of action time. CONCLUSION 5 FU may induce apoptosis in human esophageal carcinoma Eca 109 cells; ICE gene may be involved in the regulation of 5 FU induced apoptosis; and ICE protein may mediate apoptosis induced by 5 FU.

关键词： esophageal cancinoma cell line apoptosis 5 fluorouracil interleukin 1β converting enzyme

EFFECT OF ANGIOTENSIN converting ENZYME INHIBITORS ON TOLERANCE OF NITROGLYCERIN

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Chinese Medical Journal 1995年第12期 41-44页

作者：房振英李运乾刘达谨李雅菲郝菲刘卓敏

The aim of this study was to assess whether the angiotensin-converting enzyme inhibitors captopril and enalaprilat could change the tolerance of nitroglvcerin in isolated rat aortae. In aortic rings precontracted with potassium chloride, captopril (1μM) but not enalaprilat (0.1μM) incubation potentiated the responses to nitroglvcerin. It is suggested that captopril can reduce the tolerance of nitroglvcerin because it is a sulfhydryl group donor.

关键词： converting donor incubation potassium rings

Association　of　angiotensin-converting　enzyme　gene　insertion/deletion　polymorphism　with　the　clinico-pathological　manifestations　in　immunoglobulin　A　nephropathy　patients

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Chinese Medical Journal 1997年第7期 30-33页

作者：陈香美刘述文叶一舟徐启河

Objective To investigate the relationship between angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism and the clinico pathological manifestations in patients with immunoglobulin nephropathy (IgAN). Methods A flanking primer pair and an insertion specific primer pair were used to perform two polymerase chain reactions so as to analyse the insertion/deletion polymorphism of ACE gene. Results There was a significantly higher genotype fre quency for DD genotype in IgAN patients. The frequencies for DD genotype were also higher in those patients with hypertension and/or heavy proteinuria and/or severe glomerular sclerosis (P<0.05). Conclusions We observed a significant association of the deletion polymorphism of ACE gene with renal insufficiency, hypertension and severe glomerular lesions at biopsy. The deletion allele may play a role, at least to some extent, in the deterioration and progression in IgA nephropathy.

关键词： immunoglobulin converting enzyme gene Association manifestations nephropathy of patients polymorphism