title: [Advanced glycated albumin induces macrophage apoptosis via activating caspase-12 pathway].
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.
authors.affiliation: College of Basic Medical Sciences, Taishan Medical University, Taian 271000, China.
authors.forename: Jin-Guo
authors.initials: JG
authors.lastname: Li
authors.affiliation: College of Basic Medical Sciences, Taishan Medical University, Taian 271000, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hao
authors.affiliation: College of Population and Family Planning, Taishan Medical University, Taian 271000, China.
authors.forename: Ying-Xue
authors.initials: YX
authors.lastname: Liu
authors.affiliation: College of Basic Medical Sciences, Taishan Medical University, Taian 271000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: College of Basic Medical Sciences, Taishan Medical University, Taian 271000, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: College of Population and Family Planning, Taishan Medical University, Taian 271000, China.
authors.forename: Xia-Yan
authors.initials: XY
authors.lastname: Shao
authors.affiliation: Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.affiliation: College of Basic Medical Sciences, Taishan Medical University, Taian 271000, China.
authors.forename: Yong-Qi
authors.initials: YQ
authors.lastname: Fang
authors.affiliation: College of Basic Medical Sciences, Taishan Medical University, Taian 271000, China. yst228@126.com.
authors.forename: Shu-Tong
authors.initials: ST
authors.lastname: Yao
mesh_terms: D000818:Animals; D017209:Apoptosis; D053454:Caspase 12; D045744:Cell Line, Tumor; D002470:Cell Survival; D059865:Endoplasmic Reticulum Stress; D017127:Glycation End Products, Advanced; D008264:Macrophages; D051379:Mice; D010654:Phenylbutyrates; D012709:Serum Albumin; D014415:Tunicamycin; D000093423:Glycated Serum Albumin
chemical_list: D017127:Glycation End Products, Advanced; D010654:Phenylbutyrates; D012709:Serum Albumin; D014415:Tunicamycin; C075773:4-phenylbutyric acid; C506440:Casp12 protein, mouse; D053454:Caspase 12; D000093423:Glycated Serum Albumin