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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 1(2),161-170;2008
Original Article
Suppression of PGC-1α by ethanol: Implications of its role in alcohol induced liver
injury
Wayne W. Chaung, Asha Jacob, Youxin Ji and Ping Wang
Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center and The Feinstein Institute for Medical
Research, Manhasset, NY 11030
Received February 18, 2008; accepted March 20, 2008; available online March 20, 2008
Abstract: Ethanol has been known to cause injury to the liver, and other tissues; however the molecular factors responsible for alcohol
induced liver injury has not been fully understood. Recent studies indicate that reactive oxygen species (ROS) may play an important
role in alcohol induced liver injury. Peroxisome proliferator activated receptor-γ (PPAR-γ)-coactivator 1α (PGC-1α) has been shown to be
involved in defenses against ROS by inducing many ROS-detoxifying enzymes. However, the role of PGC-1α in alcohol induced liver
injury has not been elucidated. Therefore, in this study, we examined the effect of alcohol on gene and protein expression of PGC-1α in
H4-IIE cells (in vitro) and hepatic tissues (in vivo) by real-time PCR and Western blot, respectively. Our results show that exposure to
500 mM ethanol in H4-IIE cells for 24 h significantly decreased both gene and protein expression of PGC-1α. PGC-1α gene expression
was significantly decreased in cells exposed to 100 ng/ml LPS or 1% hypoxia for 24 h. In addition, PGC-1α gene and protein
expressions were slightly lower in hepatic tissues of rats exposed to ethanol for 15 h, at the level equivalent to the 500 mM used in
culture cells, in comparison to sham rats. In contrast, serum LDH and AST levels in ethanol exposed rats were 1.9 fold and 2.8 fold
higher than that of sham rats, respectively, which suggest significant organ injury in these rats following ethanol exposure. Likewise,
catalase, an enzyme that hydrolyzes peroxide to water, is significantly increased in ethanol exposed H4-IIE cells which further confirms
ROS generation due to ethanol exposure. Thus, the present study clearly indicates that ethanol suppresses PGC-1α in the liver and
that this inhibition, in part, is caused by ROS. (IJCEM802001).
Key Words: Alcohol, PGC-1α, Liver, H4-IIE cells, LPS, hypoxia
Full Text PDF
Address all correspondence to: Ping Wang, MD, Division of Surgical Research, The Feinstein Institute for Medical Research, 350
Community Drive, Manhasset, NY 11030. Tel: (516) 562-3411, Fax: (516) 562-1022; E-mail:pwang@nshs.edu.
Original Article
Suppression of PGC-1α by ethanol: Implications of its role in alcohol induced liver
injury
Wayne W. Chaung, Asha Jacob, Youxin Ji and Ping Wang
Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center and The Feinstein Institute for Medical
Research, Manhasset, NY 11030
Received February 18, 2008; accepted March 20, 2008; available online March 20, 2008
Abstract: Ethanol has been known to cause injury to the liver, and other tissues; however the molecular factors responsible for alcohol
induced liver injury has not been fully understood. Recent studies indicate that reactive oxygen species (ROS) may play an important
role in alcohol induced liver injury. Peroxisome proliferator activated receptor-γ (PPAR-γ)-coactivator 1α (PGC-1α) has been shown to be
involved in defenses against ROS by inducing many ROS-detoxifying enzymes. However, the role of PGC-1α in alcohol induced liver
injury has not been elucidated. Therefore, in this study, we examined the effect of alcohol on gene and protein expression of PGC-1α in
H4-IIE cells (in vitro) and hepatic tissues (in vivo) by real-time PCR and Western blot, respectively. Our results show that exposure to
500 mM ethanol in H4-IIE cells for 24 h significantly decreased both gene and protein expression of PGC-1α. PGC-1α gene expression
was significantly decreased in cells exposed to 100 ng/ml LPS or 1% hypoxia for 24 h. In addition, PGC-1α gene and protein
expressions were slightly lower in hepatic tissues of rats exposed to ethanol for 15 h, at the level equivalent to the 500 mM used in
culture cells, in comparison to sham rats. In contrast, serum LDH and AST levels in ethanol exposed rats were 1.9 fold and 2.8 fold
higher than that of sham rats, respectively, which suggest significant organ injury in these rats following ethanol exposure. Likewise,
catalase, an enzyme that hydrolyzes peroxide to water, is significantly increased in ethanol exposed H4-IIE cells which further confirms
ROS generation due to ethanol exposure. Thus, the present study clearly indicates that ethanol suppresses PGC-1α in the liver and
that this inhibition, in part, is caused by ROS. (IJCEM802001).
Key Words: Alcohol, PGC-1α, Liver, H4-IIE cells, LPS, hypoxia
Full Text PDF
Address all correspondence to: Ping Wang, MD, Division of Surgical Research, The Feinstein Institute for Medical Research, 350
Community Drive, Manhasset, NY 11030. Tel: (516) 562-3411, Fax: (516) 562-1022; E-mail:pwang@nshs.edu.
