Gerontoxanthone I and Macluraxanthone Induce Mitophagy and Attenuate Ischemia/Reperfusion Injury

Qian Xiang; Qian Xiang; Man Wu; Man Wu; Li Zhang; Li Zhang; Wenwei Fu; Wenwei Fu; Jinling Yang; Jinling Yang; Baojun Zhang; Baojun Zhang; Zhaoqing Zheng; Zhaoqing Zheng; Hong Zhang; Hong Zhang; Yuanzhi Lao; Yuanzhi Lao; Hongxi Xu

doi:10.3389/fphar.2020.00452

Frontiers in Pharmacology (Apr 2020)

Gerontoxanthone I and Macluraxanthone Induce Mitophagy and Attenuate Ischemia/Reperfusion Injury

Qian Xiang,
Qian Xiang,
Man Wu,
Man Wu,
Li Zhang,
Li Zhang,
Wenwei Fu,
Wenwei Fu,
Jinling Yang,
Jinling Yang,
Baojun Zhang,
Baojun Zhang,
Zhaoqing Zheng,
Zhaoqing Zheng,
Hong Zhang,
Hong Zhang,
Yuanzhi Lao,
Yuanzhi Lao,
Hongxi Xu

Affiliations

Qian Xiang: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Qian Xiang: Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Man Wu: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Man Wu: Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Li Zhang: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Li Zhang: Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Wenwei Fu: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Wenwei Fu: Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Jinling Yang: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Jinling Yang: Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Baojun Zhang: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Baojun Zhang: Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Zhaoqing Zheng: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Zhaoqing Zheng: Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Hong Zhang: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Hong Zhang: Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Yuanzhi Lao: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Yuanzhi Lao: Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Hongxi Xu: Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China

DOI: https://doi.org/10.3389/fphar.2020.00452
Journal volume & issue: Vol. 11

Abstract

Read online

Mitophagy is a crucial process in controlling mitochondrial biogenesis. Balancing mitophagy and mitochondrial functions is required for maintaining cellular homeostasis. In this study, we found that Gerontoxanthone I (GeX1) and Macluraxanthone (McX), xanthone derivatives isolated from Garcinia bracteata C. Y. Wu ex Y. H. Li, induced Parkin puncta accumulation and promoted mitophagy. GeX1 and McX treatment induced the degradation of mitophagy-related proteins such as Tom20 and Tim23. GeX1 and McX directly stabilized PTEN-induced putative kinase 1 (PINK1) on the outer membrane of the mitochondria, and then recruited Parkin to mitochondria. This significantly induced phosphorylation and ubiquitination of Parkin, suggesting that GeX1 and McX mediate mitophagy through the PINK1-Parkin pathway. Transfecting ParkinS65A or pretreated MG132 abolished the induction effects of GeX1 and McX on mitophagy. Furthermore, GeX1 and McX treatment decreased cell death and the level of ROS in an ischemia/reperfusion (IR) injury model in H9c2 cells compared to a control group. Taken together, our data suggested that GeX1 and McX induce PINK1-Parkin–mediated mitophagy and attenuate myocardial IR injury in vitro.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

About the journal

Abstract

Keywords