title: The role of molecular chaperonins in warm ischemia and reperfusion injury in the steatotic liver: a proteomic study.
abstract: BACKGROUND
  The molecular basis of the increased susceptibility of steatotic livers to warm ischemia/reperfusion (I/R) injury during transplantation remains undefined. Animal model for warm I/R injury was induced in obese Zucker rats. Lean Zucker rats provided controls. Two dimensional differential gel electrophoresis was performed with liver protein extracts. Protein features with significant abundance ratios (p < 0.01) between the two cohorts were selected and analyzed with HPLC/MS. Proteins were identified by Uniprot database. Interactive protein networks were generated using Ingenuity Pathway Analysis and GRANITE software.
  
  
  RESULTS
  The relative abundance of 105 proteins was observed in warm I/R injury. Functional grouping revealed four categories of importance: molecular chaperones/endoplasmic reticulum (ER) stress, oxidative stress, metabolism, and cell structure. Hypoxia up-regulated 1, calcium binding protein 1, calreticulin, heat shock protein (HSP) 60, HSP-90, and protein disulfide isomerase 3 were chaperonins significantly (p < 0.01) down-regulated and only one chaperonin, HSP-1 was significantly upregulated in steatotic liver following I/R.
  
  
  CONCLUSIONS
  Down-regulation of the chaperones identified in this analysis may contribute to the increased ER stress and, consequently, apoptosis and necrosis. This study provides an initial platform for future investigation of the role of chaperones and therapeutic targets for increasing the viability of steatotic liver allografts.
authors.affiliation: Department of Surgery, Washington University in St Louis, School of Medicine, St Louis, MO, USA. venkataswarupt@wudosis.wustl.edu
authors.forename: Venkataswarup
authors.initials: V
authors.lastname: Tiriveedhi
authors.forename: Kendra D
authors.initials: KD
authors.lastname: Conzen
authors.forename: Jane
authors.initials: J
authors.lastname: Liaw-Conlin
authors.forename: Gundumi
authors.initials: G
authors.lastname: Upadhya
authors.forename: James
authors.initials: J
authors.lastname: Malone
authors.forename: R Reid
authors.initials: RR
authors.lastname: Townsend
authors.forename: Robnet
authors.initials: R
authors.lastname: Kerns
authors.forename: Jianluo
authors.initials: J
authors.lastname: Jia
authors.forename: Krista
authors.initials: K
authors.lastname: Csontos
authors.forename: Sabarinathan
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Thallachallour
authors.initials: T
authors.lastname: Mohanakumar
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Anderson
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D030562:Databases, Protein; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D059865:Endoplasmic Reticulum Stress; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D018832:Molecular Chaperones / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury / Q000378:metabolism*; D015854:Up-Regulation; D052096:Warm Ischemia
chemical_list: D018832:Molecular Chaperones; D020543:Proteome