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

doi:10.1186/1471-2091-13-17

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 language	English (US)
Article number	17
Journal	BMC Biochemistry
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/1471-2091-13-17
State	Published - 2012

Bibliographical note

Funding Information:
This work was supported by grants from the NIH National Center for Research Resources P01 HL66196-01(WCC); P41 RR00954 and UL1 RR024992 (RRT); and NIH 5T32CA00962120 (KDC). The NIH did not play a role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the paper for publication. The authors thank Petra Erdmann-Gilmore and Alan E. Davis for expert technical assistance and for performing the LC-MS analysis.

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), Article 17. https://doi.org/10.1186/1471-2091-13-17

Tiriveedhi, V, Conzen, KD, Liaw-Conlin, J, Upadhya, G, Malone, J, Townsend, RR, Kerns, R, Jia, J, Csontos, K, Ramachandran, S, Mohanakumar, T, Anderson, CD & Chapman, WC 2012, 'The role of molecular chaperonins in warm ischemia and reperfusion injury in the steatotic liver: A proteomic study', BMC Biochemistry, vol. 13, no. 1, 17. https://doi.org/10.1186/1471-2091-13-17

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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.",

keywords = "Chaperonins, Endoplasmic reticulum (ER) stress, Ischemia repurfusion injury, Liver transplantation, Mass spectrometry, Two dimensional gel electrophoresis",

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

note = "Funding Information: This work was supported by grants from the NIH National Center for Research Resources P01 HL66196-01(WCC); P41 RR00954 and UL1 RR024992 (RRT); and NIH 5T32CA00962120 (KDC). The NIH did not play a role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the paper for publication. The authors thank Petra Erdmann-Gilmore and Alan E. Davis for expert technical assistance and for performing the LC-MS analysis.",

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T1 - The role of molecular chaperonins in warm ischemia and reperfusion injury in the steatotic liver

T2 - A proteomic study

AU - Tiriveedhi, Venkataswarup

AU - Conzen, Kendra D.

AU - Liaw-Conlin, Jane

AU - Upadhya, Gundumi

AU - Malone, James

AU - Townsend, R. Reid

AU - Kerns, Robnet

AU - Jia, Jianluo

AU - Csontos, Krista

AU - Ramachandran, Sabarinathan

AU - Mohanakumar, Thallachallour

AU - Anderson, Christopher D.

AU - Chapman, William C.

N1 - Funding Information: This work was supported by grants from the NIH National Center for Research Resources P01 HL66196-01(WCC); P41 RR00954 and UL1 RR024992 (RRT); and NIH 5T32CA00962120 (KDC). The NIH did not play a role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the paper for publication. The authors thank Petra Erdmann-Gilmore and Alan E. Davis for expert technical assistance and for performing the LC-MS analysis.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

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KW - Endoplasmic reticulum (ER) stress

KW - Ischemia repurfusion injury

KW - Liver transplantation

KW - Mass spectrometry

KW - Two dimensional gel electrophoresis

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

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