title: Tumor necrosis factor-alpha preconditioning attenuates liver ischemia/reperfusion injury through preserving sarco/endoplasmic reticulum calcium-ATPase function.
abstract: BACKGROUND
  Tumor necrosis factor-alpha (TNF-α) is a multifunctional cytokine. In this study, we investigated the role of TNF-α preconditioning in liver ischemia/reperfusion injury (IRI).
  
  
  METHODS
  After IRI, serum alanine aminotransferase, protein levels of SERCA-3, and Caspase-3 in liver were analyzed. In vitro study, primary hepatocytes were isolated from mice and cultured in hypoxic media with or without TNF-α. The levels of SERCA-3, Caspase-3, and intracellular calcium were evaluated after 24-h incubation. In addition, protease inhibitors were adopted to determine the role of SERCA-3 in TNF-α preconditioning.
  
  
  RESULTS
  Low dose of TNF-α preconditioning protected liver from IRI, which was described by reduced serum alanine aminotransferase, Capase-3, and elevated SERCA-3 compared with the animals without TNF-α treatment. The in vitro test confirmed the protective effect of TNF-α through maintaining homeostasis of intracellular calcium. However, the effect of TNF-α was deprived by protease inhibitors.
  
  
  CONCLUSIONS
  In this study, we demonstrated that IRI reduced SERCA-3 expression in liver. Low dose of TNF-α preconditioning protected against SERCA-3 reducing, promoted intercellular calcium storage, and attenuated liver IRI.
authors.affiliation: Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Quanrongzi
authors.initials: Q
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Wenxian
authors.initials: W
authors.lastname: Guan
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase; D053148:Caspase 3; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506950:Atp2a3 protein, mouse; D002118:Calcium
keywords: Calcium; Ischemia/reperfusion injury; SERCA-3; TNF-α