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[Advanced glycated albumin induces macrophage apoptosis via activating caspase-12 pathway.] [Article in Chinese]

LI Jin-Guo, HAO Qi, LIU Ying-Xue, LI Peng, SHAO Xia-Yan, TIAN Hua, FANG Yong-Qi , YAO Shu-Tong

College of Basic Medical Sciences； College of Population and Family Planning； Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China

Abstract

The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on the activation of caspase-12, a key molecule in endoplasmic reticulum stress (ERS)-associated apoptotic pathway, and to elucidate the underlying molecular mechanisms of macrophage apoptosis. RAW264.7 macrophages were treated with AGE-alb (2, 4 and 6 g/L), control albumin (C-alb, 4 g/L), tunicamycin (TM, 4 mg/L), or pretreated with 4-phenylbutyric acid (PBA, 5 mmol/L) for 1 h and then treated with AGE-alb (4 g/L). After incubation for 24 h, the cell viability and apoptosis were determined by using MTT assay and TUNEL detection kit, respectively. Lactate dehydrogenase (LDH) activity in media was determined by using an assay kit. The protein levels of caspase-12 were examined by Western blot analysis. The results showed that like TM (an ERS inducer), incubation with AGE-alb led to significant decrease in viability and increase in LDH activity in media and apoptotic rate in a dose-dependent manner. In addition, AGE-alb induced activation of caspase-12 especially at the concentration of 4 and 6 g/L (P < 0.01), which was similar to TM. However, PBA (an ERS inhibitor) protected RAW264.7 macrophages from AGE-alb-induced decrease in viability and increases in LDH activity and apoptosis. Moreover, PBA also inhibited the caspase-12 activation induced by AGE-alb (P < 0.05). These results suggest that AGE-alb may induce apoptosis in RAW 264.7 macrophages, and the mechanism may be related to the activation of ERS-associated apoptotic pathway mediated by caspase-12.

Key words: advanced glycated albumin; endoplasmic reticulum stress; caspase-12; Macrophage; apoptosis

Received: 2016-04-27　　Accepted: 2016-06-29

Corresponding author: 姚树桐　　E-mail: yst228@126.com

Citing This Article：

LI Jin-Guo, HAO Qi, LIU Ying-Xue, LI Peng, SHAO Xia-Yan, TIAN Hua, FANG Yong-Qi , YAO Shu-Tong. [Advanced glycated albumin induces macrophage apoptosis via activating caspase-12 pathway.] [Article in Chinese]. Acta Physiol Sin 2016; 68 (6): 733-739 (in Chinese with English abstract).