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Open Access Highly Accessed Research article

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

Venkataswarup Tiriveedhi16*, Kendra D Conzen1, Jane Liaw-Conlin1, Gundumi Upadhya1, James Malone2, R Reid Townsend23, Robnet Kerns2, Jianluo Jia1, Krista Csontos2, Sabarinathan Ramachandran1, Thallachallour Mohanakumar14, Christopher D Anderson5 and William C Chapman17*

Author affiliations

1 Department of Surgery, Washington University in St. Louis, School of Medicine, St Louis, MO, USA

2 Department of Medicine, Washington University in St. Louis, School of Medicine, St Louis, MO, USA

3 Department of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St Louis, MO, USA

4 Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St Louis, MO, USA

5 Department of Surgery, University of Mississippi Medical Center, Jackson, MS, USA

6 Department of Surgery, Washington University School of Medicine, Box 8109, 3328 CSRB, 660 S. Euclid Ave, St Louis, MO, 63110, USA

7 Department of Surgery, Washington University School of Medicine, Queeny Tower-6107 660 S. Euclid Ave, St Louis, MO, 63110, USA

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Citation and License

BMC Biochemistry 2012, 13:17  doi:10.1186/1471-2091-13-17

Published: 10 September 2012

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.

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