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| 標題: | Lipid peroxidation end product 4-hydroxy-trans-2-nonenal triggers unfolded protein response and heme oxygenase-1 expression in PC12 cells: Roles of ROS and MAPK pathways |
| 作者: | Lin, Meng-Han
Yen, Jui-Hung
Weng, Ching-Yi
Wang, Lisu
Ha, Choi-Lan
Wu, Ming-Jiuan |
| 貢獻者: | 生物科技系
食品科技系
保健營養系 |
| 關鍵字: | 4-HNE
Unfolded protein response
ER stress
HO-1
p38 MAPK |
| 日期: | 2014-01 |
| 上傳時間: | 2015-05-06 21:22:29 (UTC+8) |
| 出版者: | Elsevier Ireland Ltd |
| 摘要: | This study investigates the roles of ROS overproduction and MAPK signaling pathways in the induction of unfolded protein response (UPR) and the expression of Phase II enzymes in response to 4-hydroxy-trans-2-nonenal (4-HNE) in a neuronal-like catecholaminergic PC12 cells. Our results showed that 4-HNE triggered three canonical pathways of UPR, namely IRE1-XBP1, PERK-eIF2 alpha-ATF4 and ATF6, and induced the expression of UPR-targeted genes, GRP78, CHOP, TRB3, PUMA, and GADD34, as well as Phase II enzymes, HO-1 and GCLC. 4-HNE also induced apoptosis, intracellular calcium accumulation, caspase-3 activation, and G(0)/G(1) cell cycle arrest, which was correlated with the increased expression of GADD45 alpha. The addition of tiron, a cellular permeable superoxide scavenger, scavenged 4-HNE-mediated ROS formation, but did not alleviate cytotoxicity, or the expression of UPR-targeted genes or Phase II enzymes, indicating that ROS overproduction per se did not play a major role in 4-HNE-caused deleterious effects. HO-1 expression was attenuated by Nrf2 siRNA and chemical chaperone 4-phenylbutyrate (4-PBA), suggesting HO-1 expression was regulated by Nrf2-ARE, which may work downstream of ER stress. 4-HNE treatment promptly induced ERK, JNK and p38 MAPK activation. Addition of p38 MAPK specific inhibitor SB203580 attenuated HO-1 upregulation, but enhanced expression of CHOP, PUMA and TRB3, and cytotoxicity. These results indicate that 4-HNE-induced transient p38 MAPK activation may serve as an upstream negative regulator of ER stress and confer adaptive cytoprotection against 4-HNE-mediated cell injury. (C) 2013 Elsevier Ireland Ltd. All rights reserved. |
| 關聯: | Toxicology, v.315, pp.24-37 |
| 顯示於類別: | [ 食品科技系 ] 期刊論文
[保健營養系(所) ] 期刊論文
[生物科技系(所)] 期刊論文
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