Curcumin Inhibits the PERK-eIF2α-CHOP Pathway through Promoting SIRT1 Expression in Oxidative Stress-induced Rat Chondrocytes and Ameliorates Osteoarthritis Progression in a Rat Model
Joint Authors
Tang, Tingting
Yang, Fei
Feng, Kai
Wang, Xiaoqing
Ge, Yu-Wei
Chen, Zhaoxun
Li, Xiaodong
Liu, Zhiqing
Li, Xunlin
Li, Hui
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-16
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Oxidative stress plays a crucial role in the occurrence and development of osteoarthritis (OA) through the activation of endoplasmic reticulum (ER) stress.
Curcumin is a polyphenolic compound with significant antioxidant and anti-inflammatory activity among various diseases.
To elucidate the role of curcumin in oxidative stress-induced chondrocyte apoptosis, this study investigated the effect of curcumin on ER stress-related apoptosis and its potential mechanism in oxidative stress-induced rat chondrocytes.
The results of flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed that curcumin can significantly attenuate ER stress-associated apoptosis.
Curcumin inhibited the expression of cleaved caspase3, cleaved poly (ADP-ribose) polymerase (PARP), C/EBP homologous protein (CHOP), and glucose-regulated protein78 (GRP78) and upregulated the chondroprotective protein Bcl2 in TBHP-treated chondrocytes.
In addition, curcumin promoted the expression of silent information regulator factor 2-related enzyme 1 (SIRT1) and suppressed the expression of activating transcription factor 4 (ATF4), the ratio of p-PERK/PERK, p-eIF2α/eIF2α.
Our anterior cruciate ligament transection (ACLT) rat OA model research demonstrated that curcumin (50 mg/kg and 150 mg/kg) ameliorated the degeneration of articular cartilage and inhibited chondrocyte apoptosis in ACLT rats in a dose-dependent manner.
By applying immunohistochemical analysis, we found that curcumin enhanced the expression of SIRT1 and inhibited the expression of CHOP and cleaved caspase3 in ACLT rats.
Taken together, our present findings firstly indicate that curcumin could inhibit the PERK-eIF2α-CHOP axis of the ER stress response through the activation of SIRT1 in tert-Butyl hydroperoxide- (TBHP-) treated rat chondrocytes and ameliorated osteoarthritis development in vivo.
American Psychological Association (APA)
Feng, Kai& Ge, Yu-Wei& Chen, Zhaoxun& Li, Xiaodong& Liu, Zhiqing& Li, Xunlin…[et al.]. 2019. Curcumin Inhibits the PERK-eIF2α-CHOP Pathway through Promoting SIRT1 Expression in Oxidative Stress-induced Rat Chondrocytes and Ameliorates Osteoarthritis Progression in a Rat Model. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1205785
Modern Language Association (MLA)
Feng, Kai…[et al.]. Curcumin Inhibits the PERK-eIF2α-CHOP Pathway through Promoting SIRT1 Expression in Oxidative Stress-induced Rat Chondrocytes and Ameliorates Osteoarthritis Progression in a Rat Model. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-17.
https://search.emarefa.net/detail/BIM-1205785
American Medical Association (AMA)
Feng, Kai& Ge, Yu-Wei& Chen, Zhaoxun& Li, Xiaodong& Liu, Zhiqing& Li, Xunlin…[et al.]. Curcumin Inhibits the PERK-eIF2α-CHOP Pathway through Promoting SIRT1 Expression in Oxidative Stress-induced Rat Chondrocytes and Ameliorates Osteoarthritis Progression in a Rat Model. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1205785
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205785