Synergistic Effects of Cilostazol and Probucol on ER Stress-Induced Hepatic Steatosis via Heme Oxygenase-1-Dependent Activation of Mitochondrial Biogenesis
Joint Authors
Pandiri, Indira
Park, Jeongmin
Ryu, Jinhyun
Park, Jeong Woo
Ryter, Stefan W.
Kim, Hyo Jeong
Cho, Gyeong Jae
Chen, Yingqing
Kim, Seul-Ki
Joe, Yeonsoo
Chung, Hun Taeg
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-01-06
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
The selective type-3 phosphodiesterase inhibitor cilostazol and the antihyperlipidemic agent probucol have antioxidative, anti-inflammatory, and antiatherogenic properties.
Moreover, cilostazol and probucol can regulate mitochondrial biogenesis.
However, the combinatorial effect of cilostazol and probucol on mitochondrial biogenesis remains unknown.
Endoplasmic reticulum (ER) stress is a well-known causative factor of nonalcoholic fatty liver disease (NAFLD) which can impair mitochondrial function in hepatocytes.
Here, we investigated the synergistic effects of cilostazol and probucol on mitochondrial biogenesis and ER stress-induced hepatic steatosis.
A synergistic effect of cilostazol and probucol on HO-1 and mitochondrial biogenesis gene expression was found in human hepatocellular carcinoma cells (HepG2) and murine primary hepatocytes.
Furthermore, in an animal model of ER stress involving tunicamycin, combinatorial treatment with cilostazol and probucol significantly increased the expression of HO-1 and mitochondrial biogenesis-related genes and proteins, whereas it downregulated serum ALT, eIF2 phosphorylation, and CHOP expression, as well as the lipogenesis-related genes SREBP-1c and FAS.
Based on these results, we conclude that cilostazol and probucol exhibit a synergistic effect on the activation of mitochondrial biogenesis via upregulation of HO-1, which confers protection against ER stress-induced hepatic steatosis.
American Psychological Association (APA)
Chen, Yingqing& Pandiri, Indira& Joe, Yeonsoo& Kim, Hyo Jeong& Kim, Seul-Ki& Park, Jeongmin…[et al.]. 2016. Synergistic Effects of Cilostazol and Probucol on ER Stress-Induced Hepatic Steatosis via Heme Oxygenase-1-Dependent Activation of Mitochondrial Biogenesis. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-14.
https://search.emarefa.net/detail/BIM-1113878
Modern Language Association (MLA)
Chen, Yingqing…[et al.]. Synergistic Effects of Cilostazol and Probucol on ER Stress-Induced Hepatic Steatosis via Heme Oxygenase-1-Dependent Activation of Mitochondrial Biogenesis. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-14.
https://search.emarefa.net/detail/BIM-1113878
American Medical Association (AMA)
Chen, Yingqing& Pandiri, Indira& Joe, Yeonsoo& Kim, Hyo Jeong& Kim, Seul-Ki& Park, Jeongmin…[et al.]. Synergistic Effects of Cilostazol and Probucol on ER Stress-Induced Hepatic Steatosis via Heme Oxygenase-1-Dependent Activation of Mitochondrial Biogenesis. Oxidative Medicine and Cellular Longevity. 2016. Vol. 2016, no. 2016, pp.1-14.
https://search.emarefa.net/detail/BIM-1113878
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1113878