ERK1/2 MAPK promotes autophagy to suppress ER stress-mediated apoptosis induced by cadmium in rat proximal tubular cells

被引：39

作者：

Luo, Tongwang ^{[1
,2
,3
]}

Zhang, Huiyan ^{[1
,2
,3
]}

Yu, Qi ^{[1
,2
,3
]}

Liu, Gang ^{[1
,2
,3
]}

Long, Mengfei ^{[1
,2
,3
]}

Zhang, Kanglei ^{[1
,2
,3
]}

Liu, Wei ^{[1
,2
,3
]}

Song, Ruilong ^{[1
,2
,3
]}

Bian, Jianchun ^{[1
,2
,3
]}

Gu, Jianhong ^{[1
,2
,3
]}

Zou, Hui ^{[1
,2
,3
]}

Liu, Xuezhong ^{[1
,2
,3
]}

Yuan, Yan ^{[1
,2
,3
]}

Liu, Zongping ^{[1
,2
,3
]}

机构：

[1] Yangzhou Univ, Coll Vet Med, 12 East Wenhui Rd, Yangzhou 225009, Jiangsu, Peoples R China

[2] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China

[3] Jiangsu Key Lab Zoonosis, Yangzhou, Jiangsu, Peoples R China

来源：

TOXICOLOGY IN VITRO | 2018年 / 52卷

基金：

中国国家自然科学基金;

关键词：

ERK1/2; Cadmium; Apoptosis; ER stress; Autophagy; ENDOPLASMIC-RETICULUM STRESS; OXIDATIVE DAMAGE; EPITHELIAL-CELLS; KIDNEY; ACTIVATION; EXPRESSION; DEATH; PROLIFERATION; PATHWAY; TRANSITION;

D O I：

10.1016/j.tiv.2018.06.001

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Cadmium (Cd) is a toxic heavy metal and its toxic mechanism is not entirely clear. The goal of the present study was to investigate the toxic mechanism of Cd on rPT cells, and to elucidate the role of ERK1/2 signaling pathway in mediating the relationship between apoptosis and autophagy. We evaluated the cell morphology, cell cycle distribution, apoptosis rates, and the expression of related proteins. We observed that increased Cd concentration disrupted cell morphology, increased apoptosis and induced autophagy. Additionally, activation of JNK1/2 and p38 MAPK promoted apoptosis, while activation of ERK1/2 inhibited apoptosis. Upon inhibition of autophagy, apoptosis rate and the expression of ER proteins related to the apoptosis were increased. Following inhibition of the ERK1/2 signaling pathway, the number of LC3 aggregates, the rate of LC3II/LC3I and the expression of Beclin-1were decreased, but the expression level of ER proteins related to apoptosis were increased. Our results indicated that Cd exposure damages cells also induces apoptosis and autophagy, meanwhile demonstrate that the ERK1/2 signaling pathway plays an important role in this process. Besides, these data suggest that autophagy can inhibit Cd-induced apoptosis and the ERK1/2 signaling pathway can suppress ER stress-mediated apoptosis by activating autophagy.

引用

页码：60 / 69

页数：10

共 53 条

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