Involvement of NADPH oxidases and non-muscle myosin light chain in senescence of endothelial progenitor cells in hyperlipidemia
Involvement of NADPH oxidases and non-muscle myosin light chain in senescence of endothelial progenitor cells in hyperlipidemia
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NADPH氧化酶和非肌肉肌球蛋白轻链参与高脂血症内皮祖细胞衰老
DOI：
10.1007/s00210-015-1198-y
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发表时间：
2015-12
影响因子：
3.6
通讯作者：
Peng Jun
中科院分区：
文献类型：
--
作者：
Li Ting-Bo;Zhang Jie-Jie;Liu Bin;Liu Wei-Qi;Wu Yan;Xiong Xiao-Ming;Luo Xiu-Ju;Ma Qi-Lin;Peng Jun
NADPH oxidase (NOX)-derived reactive oxygen species (ROS) is involved in endothelial dysfunction of hyperlipidemia, and non-muscle myosin regulatory light chain (nmMLC20) is reported to have a transcriptional function in regulation of gene expression. The purposes of this study are to determine whether NOX-derived ROS can promote endothelial progenitor cell (EPC) senescence and whether nmMLC20can regulate NOX expression through a phosphorylation-dependent manner. The rats were subjected to 8 weeks of high-fat diet feeding to establish a hyperlipidemic model, which showed an increase in plasma lipids and the accelerated senescence and reduced number of circulating EPCs, accompanied by an increase in myosin light chain kinase (MLCK) and NOX activities, p-nmMLC20level, NOX (NOX2, NOX4) expression, and H2O2content. Next, EPCs isolated from normal rats were incubated with ox-LDL (100 μg/mL) for 24 h to establish a senescent model in vitro. Consistent with our in vivo findings, ox-LDL treatment increased the senescence of EPCs concomitant with an increase in MLCK and NOX activities, p-nmMLC20level (in total or nuclear proteins), NOX expression, and H2O2content; these phenomena were reversed by MLCK inhibitor. NOX inhibitor achieved similar results to that of MLCK inhibitor except that there is no effect on MLCK activity and p-nmMLC20level. Furthermore, knockdown of nmMLC20, NOX2, or NOX4 led to a down-regulation in NOX and a reduction in ox-LDL-induced EPC senescence. These results suggest that NOX-derived ROS promotes the senescence of circulating EPCs in hyperlipidemia and nmMLC20may play a transcriptional role in the upregulation of NOX through a phosphorylation-dependent manner.
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影响因子：
37.8
作者：
Sun C;Wu MH;Yuan SY
通讯作者：
Yuan SY
影响因子：
7.4
作者：
Zhang H;Davies KJA;Forman HJ
通讯作者：
Forman HJ
影响因子：
6.6
作者：
Gerrits, Lieke;Overheul, Gijs J.;Wansink, Derick G.
通讯作者：
Wansink, Derick G.
影响因子：
2.1
作者：
Vemparala K;Roy A;Bahl VK;Prabhakaran D;Nath N;Sinha S;Nandi P;Pandey RM;Reddy KS;Manhapra A;Lakshmy R
通讯作者：
Lakshmy R
高血压内皮祖细胞加速衰老与降钙素基因相关肽减少有关
影响因子：
4.9
作者：
Chang-Ping Hu;Xiao-Ping Chen;Zhi Zhou;Ting-Ting Li;Dai li;Chen-Jing Wang;Yuan-Jian Li;Jun Peng
通讯作者：
Jun Peng