The role of molecular chaperonins in warm ischemia and reperfusion injury in the steatotic liver: A proteomic study

作者：Tiriveedhi Venkataswarup^*; Conzen Kendra D; Liaw Conlin Jane; Upadhya Gundumi; Malone James; Townsend R Reid; Kerns Robnet; Jia Jianluo; Csontos Krista; Ramachandran Sabarinathan; Mohanakumar Thallachallour; Anderson Christopher D; Chapman William C

来源：BMC Biochemistry, 2012, 13: 17.

DOI：10.1186/1471-2091-13-17

• Ischemia repurfusion injury
• Two dimensional gel electrophoresis
• Mass spectrometry
• Liver transplantation
• Chaperonins
• Endoplasmic reticulum (ER) stress

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 %26lt; 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. %26lt;br%26gt;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 %26lt; 0.01) down-regulated and only one chaperonin, HSP-1 was significantly upregulated in steatotic liver following I/R. %26lt;br%26gt;Conclusion: 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.

• 出版日期2012-9-10