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Nicotine increases apoptosis in HUVECs cultured in high glucose/high fat via Akt ubiquitination and degradation
Author(s) -
Cao Xiaofang,
Han Chunling,
Wen Jinsuo,
Guo Xiaokun,
Zhang Kejian
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12865
Subject(s) - apoptosis , protein kinase b , nicotine , viability assay , chemistry , endothelial stem cell , umbilical vein , microbiology and biotechnology , pharmacology , biology , medicine , biochemistry , in vitro
Summary It is well‐documented that nicotine, the main active ingredient in cigarettes, results in endothelial cell injury in numerous diseases. However, whether nicotine plays a crucial role in endothelial cell injury in diabetes and the exact molecular mechanism that mediates this process have not been fully elucidated. The current study aimed to investigate the effects of nicotine on endothelial cell injury in diabetes and the specific molecular mechanism by which it plays a role. Human umbilical vein endothelial cells ( HUVEC s) were incubated in HG / HF media and treated with nicotine, PYR ‐41 (a selective ubiquitin E1 inhibitor), Akt‐overexpressing adenovirus, or TTC 3 and MUL 1 sh RNA adenovirus. Cell viability was subsequently detected by the CCK 8 assay, and apoptosis was examined by caspase‐3 cleavage and activity analysis. Compared to the HG / HF incubated group, nicotine incubation significantly decreased cell survival and increased apoptosis. Moreover, nicotine induced Akt degradation via UPS , and Akt overexpression blocked nicotine‐induced apoptosis in HUVEC s cultured in HG / HF media. Furthermore, the TTC 3 and MUL 1 sh RNA adenovirus dramatically decreased the Akt ubiquitination and apoptosis induced by nicotine. These results indicate that nicotine‐induced Akt ubiquitination and degradation occurs through TTC 3 and MUL 1 and results in a dramatic increase in apoptosis in HUVEC s cultured in HG / HF media.