Inhibitory effects of L-carnitine on high glucose-induced apoptosis of HAECs by suppressing ATF6 signaling
10.3969/j.issn.1000-4718.2017.08.017
- VernacularTitle:左卡尼汀通过内质网应激ATF6通路抑制高糖诱导的HAECs凋亡
- Author:
Hongmin GAO
;
Shangjian LI
;
Huolan ZHU
;
Yu YANG
;
Zhongwei LIU
- Keywords:
L-Carnitine;
Endoplasmic reticulum stress;
Activating transcription factor 6;
Apoptosis;
Human aortic endothelial cells
- From:
Chinese Journal of Pathophysiology
2017;33(8):1449-1454
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the inhibitory effect of L-carnitine on high glucose-induced apoptosis of human aortic endothelial cells (HAECs) and the molecular mechanisms.METHODS: The apoptosis of HAECs was induced by high-glucose incubation.HAECs were treated with L-carnitine at different concentrations (50, 100 and 200 μmol/L).The cell viability was measured by MTT assay.The cell apoptosis was assessed by Hoechst 33258 staining and flow cytometry.Colorimetric method was employed to detect the caspase-3 activity in the HAECs.The protein expression and phosphorylation levels were determined by Western blot.RESULTS: High-glucose incubation dramatically decreased the cell viability and induced apoptosis.The protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme-1 (IRE1) and activating transcription factor 6 (ATF6) signaling pathways of endoplasmic reticulum stress were activated to induce cell apoptosis via down-stream caspase-4/3 cascade.However, L-carnitine treatment significantly attenuated the cell apoptosis and increased the cell viability in a concentration-dependent manner.L-carnitine also significantly suppressed endoplasmic reticulum stress and ATF6 signaling in high glucose-incubated HAECs without attenuating PERK and IRE1 signaling.The expression of site-1 protease (S1P) and site-2 protease (S2P) was inhibited by L-carnitine treatment, thus decreasing pro-apoptotic factor ATF6 p50 produced by ATF6 cleavage.CONCLUSION: L-carnitine inhibits high glucose-induced apoptosis of HAECs by inhibiting ATF6 signaling.
