title: Promotion of mitochondrial energy metabolism during hepatocyte apoptosis in a rat model of acute liver failure.
abstract: Hepatocyte apoptosis and energy metabolism in mitochondria have an important role in the mechanism of acute liver failure (ALF). However, data on the association between apoptosis and the energy metabolism of hepatocytes are lacking. The current study assessed the activity of several key enzymes in mitochondria during ALF, including citrate synthase (CS), carnitine palmitoyltransferase‑1 (CPT‑1) and cytochrome c oxidase (COX), which are involved in hepatocyte energy metabolism. A total of 40 male Sprague‑Dawley rats were divided into five groups and administered D‑galactosamine and lipopolysaccharide to induce ALF. Hepatic pathology and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling examinations indicated that hepatocyte apoptosis was observed at 4 h and increased 8 h after ALF. Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion. The results measured by electron microscopy indicated that ultrastructural changes in mitochondria began at 4 h and the mitochondrial outer membrane was completely disrupted at 24 h resulting in mitochondrial collapse. The expression of CS, CPT‑1 and COX was measured and analyzed using assay kits. The activity and protein expression of CS, CPT‑1 and COX began to increase at 4 h, reached a peak at 8 h and decreased at 12 h during ALF. The activities of CS, CPT‑1 and COX were enhanced during hepatocyte apoptosis suggesting that these enzymes are involved in the initiation and development of ALF. Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy‑consuming procedure. The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF.
authors.affiliation: The Second Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Chen
authors.affiliation: The Second Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
authors.forename: Baoshan
authors.initials: B
authors.lastname: Yang
authors.affiliation: Beijing Artificial Liver Treatment and Training Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Beijing Artificial Liver Treatment and Training Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
authors.affiliation: Beijing Artificial Liver Treatment and Training Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Duan
authors.affiliation: The Fourth Department of Infectious Diseases, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Ying-Ji
authors.initials: YJ
authors.lastname: Ma
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005688:Galactosamine / Q000633:toxicity; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D008070:Lipopolysaccharides; D005688:Galactosamine; D003576:Electron Transport Complex IV; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin