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

Venkataswarup Tiriveedhi, Kendra D. Conzen, Jane Liaw-Conlin, Gundumi Upadhya, James Malone, R. Reid Townsend, Robnet Kerns, Jianluo Jia, Krista Csontos, Sabarinathan Ramachandran, Thallachallour Mohanakumar, Christopher D. Anderson, William C. Chapman

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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-1was significantly upregulated in steatotic liver following I/R. 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.

Original languageEnglish (US)
Article number17
JournalBMC Biochemistry
Volume13
Issue number1
DOIs
StatePublished - 2012

Keywords

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

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    Tiriveedhi, V., Conzen, K. D., Liaw-Conlin, J., Upadhya, G., Malone, J., Townsend, R. R., Kerns, R., Jia, J., Csontos, K., Ramachandran, S., Mohanakumar, T., Anderson, C. D., & Chapman, W. C. (2012). The role of molecular chaperonins in warm ischemia and reperfusion injury in the steatotic liver: A proteomic study. BMC Biochemistry, 13(1), [17]. https://doi.org/10.1186/1471-2091-13-17