1. KEAP1-NRF2 complex in ischemia-induced hepatocellular damage of mouse liver transplants
- Author
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Ke, Bibo, Shen, Xiu-Da, Zhang, Yu, Ji, Haofeng, Gao, Feng, Yue, Shi, Kamo, Naoko, Zhai, Yuan, Yamamoto, Masayuki, Busuttil, Ronald W, and Kupiec-Weglinski, Jerzy W
- Subjects
Organ Transplantation ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Digestive Diseases ,Transplantation ,Underpinning research ,1.1 Normal biological development and functioning ,Inflammatory and immune system ,Oral and gastrointestinal ,Adaptor Proteins ,Signal Transducing ,Animals ,Cytoskeletal Proteins ,Hypoxia-Inducible Factor 1 ,alpha Subunit ,Kelch-Like ECH-Associated Protein 1 ,Liver ,Liver Transplantation ,Macrophages ,Male ,Mice ,Mice ,Inbred C57BL ,NF-E2-Related Factor 2 ,Neutrophils ,Phosphatidylinositol 3-Kinases ,Proto-Oncogene Proteins c-akt ,Reperfusion Injury ,Signal Transduction ,Liver ischemia/reperfusion injury ,Liver transplantation ,Keap1-Nrf2 redox system ,HO-1 ,ARE ,H(2)O(2) ,HIF-1 ,HKO ,HRE ,IRI ,Keap1 ,Kelch-like ECH-associated protein 1 ,LDH ,Nrf2 ,OLT ,PI3K ,TUNEL ,Trx1 ,anti-oxidant response element ,heme-oxygenase-1 ,hepatocyte knockout ,hydrogen peroxide ,hypoxia inducible factor-1 ,hypoxia response element ,ischemia/reperfusion injury ,lactate dehydrogenase ,nuclear factor erythroid 2-related factor 2 ,orthotopic liver transplantation ,phosphoinositide 3-kinase ,sALT ,serum alanine aminotransferase ,terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling ,thioredoxin 1 ,Clinical Sciences ,Public Health and Health Services ,Gastroenterology & Hepatology - Abstract
Background & aimsThe Keap1-Nrf2 signaling pathway regulates host cell defense responses against oxidative stress and maintains the cellular redox balance.MethodsWe investigated the function/molecular mechanisms by which Keap1-Nrf2 complex may influence liver ischemia/reperfusion injury (IRI) in a mouse model of hepatic cold storage (20h at 4°C) followed by orthotopic liver transplantation (OLT).ResultsThe Keap1 hepatocyte-specific knockout (HKO) in the donor liver ameliorated post-transplant IRI, evidenced by improved hepatocellular function and OLT outcomes (Keap1 HKO→Keap1 HKO; 100% survival), as compared with controls (WT→WT; 50% survival; p
- Published
- 2013