The hepatoprotective effects of adenine nucleotide translocator-2 against aging and oxidative stress.
Mitochondrial adenine nucleotide translocator (ANT) plays important roles in the regulation of mitochondrial permeability transition and cell bioenergetics. The mouse has three ANT isoforms (1, 2 and 4) showing tissue-specific expression patterns. Although ANT1 is known to have a pro-apoptotic property, the specific functions of ANT2 have not been well determined. In the present study, ANT2 expression was significantly lower in the aged rat liver and in a liver fibrosis model. To explore the protective role of ANT2 in the liver, we established a hepa1c1c7 cell line overexpressing ANT2. Overexpression of ANT2 caused hepa1c1c7 cells to be more resistant to oxidative stress, and mitochondrial membrane potential (MMP, ∆Ψm) was relatively intact in ANT2-overexpressing cells under oxidative stress. In addition, ANT2 was found to increase ATP production by influencing mitochondrial bioenergetics. These results imply that the hepatoprotective effect of ANT2 is due to the stabilization of MMP and enhanced ATP production, and thus, maintaining ANT2 levels in the liver might be important to enhance resistance to aging and oxidative stress.
Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Republic of Korea.
Hyun Soo
HS
Kim
Jeong Hwan
JH
Je
Tae Gen
TG
Son
Hee Ra
HR
Park
Seung Taek
ST
Ji
Yuba Raj
YR
Pokharel
Hyun Min
HM
Jeon
Keon Wook
KW
Kang
Ho Sung
HS
Kang
Seung-Cheol
SC
Chang
Hyung Sik
HS
Kim
Hae Young
HY
Chung
Jaewon
J
Lee
D033742:Adenine Nucleotide Translocator 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D014162:Transfection
D033742:Adenine Nucleotide Translocator 2; D017382:Reactive Oxygen Species