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A PKC-beta inhibitor prompts the HUVECs apoptosis-induced by advanced glycation end products.
MedLine Citation:
PMID:  22204135     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The accumulation of advanced glycation end products (AGEs) on micro-vasculature has been demonstrated to be a key factor in diabetes mellitus development. Evidence suggests that AGEs triggered apoptotic changes in human umbilical vein endothelial cells (HUVECs) and protein kinase C (PKC)-beta plays a pivotal role in AGEs-induced micro-vascular dysfunction. Thus the effect of the selective PKC-beta inhibitor (LY333531) on AGEs-induced HUVEC apoptosis and proliferation was investigated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to determine the cells viability after being incubated with AGEs and LY333531. Acridine orange/ethidium bromide (AO/EB) fluorescence detection was applied to observe the pro-apoptosis effects of AGEs and LY333531. Bcl-2, Bax and Bad proteins' expression were determined by StreptAvidin-Biotin-enzyme Complex (SABC) immunocytochenistry. The results showed that pretreatment with LY333531 strikingly decreased the chance of HUVEC survival and the effect of LY333531 on apoptotic cell death in HUVEC significantly increased compared with the AGEs group. Blockade of PKC-beta up-regulated the expression of Bax and Bad proteins and down- regulated the expression of Bcl-2 protein. Moreover, LY333531 reduced the ratio of Bcl-2/Bax. The results indicate that the selective PKC-beta inhibitor, LY333531, can further prompt AGEs-induced endothelial cells apoptosis. The increased expression of Bax, Bad and decreased expression of Bcl-2 and Bcl-2/Bax ratio are associated with the apoptotic process.
Authors:
Shan-Shan Wang; You-Hua Xu; Liang Feng; Quan Zhu; Bao He
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Die Pharmazie     Volume:  66     ISSN:  0031-7144     ISO Abbreviation:  Pharmazie     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-12-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9800766     Medline TA:  Pharmazie     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  881-7     Citation Subset:  IM    
Affiliation:
Biotechnology Laboratory for Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, P.R. China.
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