Metallothionein inhibits homocysteine-induced proliferation of rat vascular smooth muscle cells |
| |
Authors: | CAO Jun JIANG Zhi-sheng QI Yong-fen GAO Lin TANG Chao-shu DU Jun-bao |
| |
Institution: | 1. Institute of Cardiovascular Disease Research, the First Hospital, Peking University, Beijing 100034, China;
2. Department of Pathophysiology, Ning Xia Medical College, Yinchuan 750004, China |
| |
Abstract: | AIM:To investigate the effect of metallothionein(MT) on proliferation of rat vascular smooth muscle cells (VSMCs) stimulated by homocysteine and its mechanism. METHODS:VSMCs proliferation was measured by 3-H]-TdR incorporation, mitogen-activated protein kinase(MAPK)activity were determined by immunoprecipitation method, the intracellular contents of MT and malondialdehyde (MDA)were assayed by -hemoglobin saturation method and TBA reaction, respectively, and lactate dehydrogenase (LDH) leakage was measured by NADH oxidation. RESULTS:Hcy(10-6-10-4 mmol/L) stimulated 3-H]-TdR incorporation by the VSMCs in a concentration-dependent manner. Compared with control, 3-H]-TdR incorporation in VSMCs treated with 0.1 mmol/L Hcy was increased by 4.2 fold (P<0.01). Meanwhile, Hcy enhanced MAPK activity, MDA formation and LDH release (P<0.01)in a concentration-dependent manner. Treatment of VSMCs with MT alone did not change above parameters, compared with control. However, MT (10-6-10-4 mol/L)attenuated significantly Hcy-stimulated proliferation of VSMCs (P<0.01)in a concentration-dependent manner. And MT inhibited obviously Hcy-induced activation of MAPK activity, MDA formation and LDH release. Preincubation of VSMCs with 0.5 mmol/L ZnCl2 for 6 h induced an increase cellular MT content by 5.7-fold (P<0.01). The MT-overexpressed VSMCs resisted Hcy-stimulating action on MAPK activity, MDA formation and LDH leakage (P<0.01). CONCLUSION:These results show that MT has an inhibitory effect on Hcy-induced VSMCs proliferation, and that MT could inhibit Hcy-stimulated MAPK activity and lipid peroxidation. |
| |
Keywords: | Metallothionein Homocysteine Muscle smooth vascular Cells Rats |
|
| 点击此处可从《园艺学报》浏览原始摘要信息 |
| 点击此处可从《园艺学报》下载免费的PDF全文 |
|