| Objective:To elucidate the signal transduction pathway of cultured hamster aortic smooth muscle cells (SMCs) proliferation induced by advanced glycation endproducts (AOEs) and the possible role of AGEs on the diabetes macrovascular complications, we studied the effects of AGEs on the proliferation of SMCs and protein kinase C (PKC) activities.Methods:(1) AGEs were prepared in vitro by incubating bovine serum albumin (BSA)with glucose. We measured the flurescent intensity of AGEs-BSA by spectrofluorophotometer.(2) Proliferation of SMCs of Sprague-Dawley(SD) hamster were determinated by cell counting ,3-(4,5-dimethythiazo(-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 3H-thymidine ( 3H-TdR)incorporation after treatment with AGEs-BSA or PKC inhibitor.(3) By the method of enzyme-linked immunosorbent assay (ELISA),we observed the influence of AGEs-BSA on the PKC activities of particulate fraction and cytosolic fractions.Results:(1) Fluorescent intensity of AGEs-BSA raised with the improvement of glucose concentrations and glycated duration .(2) All of cell counting ,MTT and 3H-TdR incorporation showed that when glucoselevels increased and glycated duration prolonged ,the proliferation of SMCs was accelerated and there were time-dependent and dose-dependent relation between AGEs-BSA and cell numbers of SMCs. PKC inhibitor could markedly suppress SMCs proliferation.(3) On the conditions of AGEs-BSA prepared by the higher glucose concentrations for the longer glycated duration ,PKC activities of particulate fractions were higher and PKC activities of cytosolic fractions were lower.Conclusions:A possible involvement of PKC activated had been showed in vascular SMCs proliferation stimulated by AGEs, which became stronger with the improvement of glucose concentrations and glycated duration.lt suggested that for the patients of diabetes ,the higher glucose level, the longer disease course, the more AGEs could form , perhaps the higher risk of diabetes macrovascular complications.
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