Novel PGC-1αATF5 Axis Partly Activates UPRmt and Mediates Cardioprotective Role of Tetrahydrocurcumin in Pathological Cardiac Hypertrophy
Joint Authors
Feng, Pan
Duan, Weixun
Wang, Xiaowu
Liu, Jincheng
Zhang, Bing
Wang, Qian
Ding, Wenyuan
Tan, Yanzhen
Zhang, Zhengbin
Yi, Dinghua
Sun, Yang
Yi, Wei
Liang, Hongliang
Yu, Shiqiang
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-21, 21 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-12-28
Country of Publication
Egypt
No. of Pages
21
Main Subjects
Abstract EN
Mitochondrial unfolding protein response (UPRmt) effectively resists the pathological cardiac hypertrophy and improves the mitochondrial function.
However, the specific activation mechanism and drugs that can effectively activate UPRmt in the cardiac muscle are yet to be elucidated.
The aim of this study was to determine the regulation role of UPRmt on preventing pathological cardiac hypertrophy by tetrahydrocurcumin (THC) and explore its underlying molecular mechanism.
Male C57BL/6J wild-type (WT) mice were divided into a control group and subjected to sham treatment for 4 weeks, and a test group which was subjected to transverse aortic constriction (TAC) surgery.
Animals in the control and test group were orally administered THC (50 mg/kg) for 4 weeks after TAC procedure; an equivalent amount of saline was orally administered in the control sham-treated group and the TAC group.
Subsequently, oxidative stress and UPRmt markers were assessed in these mice, and cardiac hypertrophy, fibrosis, and cardiac function were tested.
Small interfering RNA (siRNA) targeting proliferator-activated receptor-gamma coactivator (PGC)-1α and activating transcription factor 5 (ATF5) were used to determine the UPRmt activation mechanism.
THC supplement partly upregulated UPRmt effectors and inhibited TAC-induced oxidative stress compared with TAC-operated WT mice, thereby substantially attenuating contractile dysfunction, cardiac hypertrophy, and fibrosis.
Furthermore, PGC-1α knockdown blunted the UPRmt activation and the cardioprotective role of THC.
The interaction between PGC-1α and ATF5 was tested in neonatal rat cardiac myocytes under normal conditions.
The results showed that PGC-1α was an upstream effector of ATF5 and partly activated UPRmt.
In vitro, phenylephrine- (PE-) induced cardiomyocyte hypertrophy caused ATF5 upregulating rather than downregulating corresponding to the downregulation of PGC-1α.
The PGC-1α/ATF5 axis mediated the UPRmt activation and stress-resistance role of THC in vitro.
Collectively, the present study provides the first evidence that PGC-1 and ATF5 can form a signaling axis to partly activate UPRmt that mediates the cardioprotective role of THC in pathological cardiac hypertrophy.
American Psychological Association (APA)
Zhang, Bing& Tan, Yanzhen& Zhang, Zhengbin& Feng, Pan& Ding, Wenyuan& Wang, Qian…[et al.]. 2020. Novel PGC-1αATF5 Axis Partly Activates UPRmt and Mediates Cardioprotective Role of Tetrahydrocurcumin in Pathological Cardiac Hypertrophy. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-21.
https://search.emarefa.net/detail/BIM-1205972
Modern Language Association (MLA)
Zhang, Bing…[et al.]. Novel PGC-1αATF5 Axis Partly Activates UPRmt and Mediates Cardioprotective Role of Tetrahydrocurcumin in Pathological Cardiac Hypertrophy. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-21.
https://search.emarefa.net/detail/BIM-1205972
American Medical Association (AMA)
Zhang, Bing& Tan, Yanzhen& Zhang, Zhengbin& Feng, Pan& Ding, Wenyuan& Wang, Qian…[et al.]. Novel PGC-1αATF5 Axis Partly Activates UPRmt and Mediates Cardioprotective Role of Tetrahydrocurcumin in Pathological Cardiac Hypertrophy. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-21.
https://search.emarefa.net/detail/BIM-1205972
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205972