Necrostatin-1 ameliorates adjuvant arthritis rat articular chondrocyte injury via inhibiting ASIC1a-mediated necroptosis

被引：40
作者：
Chen, Yong [1 ,2 ]
Zhu, Chuan-Jun [1 ,2 ]
Zhu, Fei [1 ,2 ]
Dai, Bei-Bei [1 ,2 ]
Song, Su-Jing [1 ,2 ]
Wang, Zhi-Qiang [1 ,2 ]
Feng, Yu-Bin [1 ,2 ]
Ge, Jin-Fang [1 ,2 ]
Zhou, Ren-Peng [3 ]
Chen, Fei-Hu [1 ,2 ]
机构：
[1] Anhui Med Univ, Sch Pharm, Anhui Key Lab Bioact Nat Prod, Hefei 230032, Anhui, Peoples R China
[2] Anhui Med Univ, Key Lab Antiinflammatory & Immune Med, Minist Educ, Hefei 230032, Anhui, Peoples R China
[3] Anhui Med Univ, Dept Pharmacol, Hosp 2, Hefei 230601, Anhui, Peoples R China
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2018年 / 504卷 / 04期
基金：
美国国家科学基金会;
关键词：
ASIC1a; Necroptosis; Rheumatoid arthritis; RIP1; RIP3; Acidosis; SENSING ION CHANNELS; PROGRAMMED NECROSIS; CELL-DEATH; TNF-ALPHA; APOPTOSIS; CALCIUM; KINASE; EXPRESSION; INCREASES; AUTOPHAGY;
D O I：
10.1016/j.bbrc.2018.09.031
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Necroptosis, a necrotic cell death pathway regulated by receptor interacting protein (RIP) 1 and 3, plays a key role in pathophysiological processes, including rheumatoid arthritis (RA). However, whether necroptosis is involved in RA articular cartilage damage processes remain unclear. The aim of present study was to investigate the dynamic changes in arthritic chondrocyte necroptosis and the effect of RIP1 inhibitor necrostatin-1 (Nec-1) and acid-sensing ion channels (ASICs) inhibitor amiloride on arthritic cartilage injury and acid-induced chondrocyte necroptosis. Our results demonstrated that the expression of RIP1, RIP3 and mixed lineage kinase domain-like protein phosphorylation (p-MLKL) were increased in adjuvant arthritis (AA) rat articular cartilage in vivo and acid-induced chondrocytes in vitro. High co-expression of ASIC1a and RIP1 showed in AA rat articular cartilage. Moreover, Nec-1 and amiloride could reduce articular cartilage damage and necroinflammation in AA rats. In addition, acid-induced increase in necroptosis markers RIP1/RIP3 were inhibited by Nec-1, ASIC1a-specific blocker psalmotoxin-1 (PcTx-1) or ASIC1a-short hairpin RNA respectively, which revealed that necroptosis is triggered in acid-induced chondrocytes and mediated by ASIC1a. These findings indicated that blocking ASIC1a-mediated chondrocyte necroptosis may provide potential therapeutic strategies for RA treatment. (C) 2018 Elsevier Inc. All rights reserved.
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收藏
页码：843 / 850
页数：8
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