Improved islet yields from pancreas preserved in perflurocarbon is via inhibition of apoptosis mediated by mitochondrial pathway

S. Ramachandran, Niraj M Desai, T. A. Goers, N. Benshoff, B. Olack, S. Shenoy, M. D. Jendrisak, W. C. Chapman, T. Mohanakumar

Research output: Contribution to journalArticle

Abstract

Islet transplantation is a treatment option for type I diabetic patients. Preservation of human pancreata prior to islet isolation using two-layer method with perfluorocarbon (PFC) and University of Wisconsin solution (UW) results in twofold increase in islet yields. The objective of this study was to determine the mechanism by which islets undergo apoptosis and determine PFC's effects on this process. Gene array analysis was used to analyze the expression of pro- and anti-apoptotic genes in islets isolated from pancreata preserved under varying conditions. A 12-fold increase in the expression of inhibitor of apoptosis (IAP) and survivin was observed in islets isolated from pancreata preserved in PFC. This was accompanied by decreased expression of BAD (3.7-fold), BAX (2.7-fold) and caspases (5.2-fold). Levels of activated caspase-9 (77.98%), caspase-2 (61.5%), caspase-3 (68.3%) and caspase-8 (37.2%) were also reduced. 'Rescue' of pancreata after storage (12 h) in UW by preservation using PFC also resulted in a down-regulation of pro-apoptotic genes and inhibition of caspase activation. Apoptosis observed in islets from all groups was mainly mitochondria-dependent, mediated by change in redox potential initiated by hypoxia. We demonstrate that reduction in hypoxia of pancreata preserved using PFC leads to significant up-regulation of anti-apoptotic and inhibition of pro-apoptotic genes.

Original languageEnglish (US)
Pages (from-to)1696-1703
Number of pages8
JournalAmerican Journal of Transplantation
Volume6
Issue number7
DOIs
StatePublished - Jul 2006
Externally publishedYes

Fingerprint

Fluorocarbons
Pancreas
Apoptosis
Caspases
Genes
Caspase 2
Islets of Langerhans Transplantation
Caspase 9
Caspase 8
Caspase 3
Oxidation-Reduction
Mitochondria
Up-Regulation
Down-Regulation
Hypoxia
Therapeutics

Keywords

  • Apoptosis
  • Islets
  • Mitochondria-dependent
  • PFC
  • Preservation

ASJC Scopus subject areas

  • Immunology

Cite this

Improved islet yields from pancreas preserved in perflurocarbon is via inhibition of apoptosis mediated by mitochondrial pathway. / Ramachandran, S.; Desai, Niraj M; Goers, T. A.; Benshoff, N.; Olack, B.; Shenoy, S.; Jendrisak, M. D.; Chapman, W. C.; Mohanakumar, T.

In: American Journal of Transplantation, Vol. 6, No. 7, 07.2006, p. 1696-1703.

Research output: Contribution to journalArticle

Ramachandran, S, Desai, NM, Goers, TA, Benshoff, N, Olack, B, Shenoy, S, Jendrisak, MD, Chapman, WC & Mohanakumar, T 2006, 'Improved islet yields from pancreas preserved in perflurocarbon is via inhibition of apoptosis mediated by mitochondrial pathway', American Journal of Transplantation, vol. 6, no. 7, pp. 1696-1703. https://doi.org/10.1111/j.1600-6143.2006.01368.x
Ramachandran, S. ; Desai, Niraj M ; Goers, T. A. ; Benshoff, N. ; Olack, B. ; Shenoy, S. ; Jendrisak, M. D. ; Chapman, W. C. ; Mohanakumar, T. / Improved islet yields from pancreas preserved in perflurocarbon is via inhibition of apoptosis mediated by mitochondrial pathway. In: American Journal of Transplantation. 2006 ; Vol. 6, No. 7. pp. 1696-1703.
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AU - Desai, Niraj M

AU - Goers, T. A.

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AU - Olack, B.

AU - Shenoy, S.

AU - Jendrisak, M. D.

AU - Chapman, W. C.

AU - Mohanakumar, T.

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AB - Islet transplantation is a treatment option for type I diabetic patients. Preservation of human pancreata prior to islet isolation using two-layer method with perfluorocarbon (PFC) and University of Wisconsin solution (UW) results in twofold increase in islet yields. The objective of this study was to determine the mechanism by which islets undergo apoptosis and determine PFC's effects on this process. Gene array analysis was used to analyze the expression of pro- and anti-apoptotic genes in islets isolated from pancreata preserved under varying conditions. A 12-fold increase in the expression of inhibitor of apoptosis (IAP) and survivin was observed in islets isolated from pancreata preserved in PFC. This was accompanied by decreased expression of BAD (3.7-fold), BAX (2.7-fold) and caspases (5.2-fold). Levels of activated caspase-9 (77.98%), caspase-2 (61.5%), caspase-3 (68.3%) and caspase-8 (37.2%) were also reduced. 'Rescue' of pancreata after storage (12 h) in UW by preservation using PFC also resulted in a down-regulation of pro-apoptotic genes and inhibition of caspase activation. Apoptosis observed in islets from all groups was mainly mitochondria-dependent, mediated by change in redox potential initiated by hypoxia. We demonstrate that reduction in hypoxia of pancreata preserved using PFC leads to significant up-regulation of anti-apoptotic and inhibition of pro-apoptotic genes.

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