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Transplantation. 2017 Mar;101(3):e59-e67. doi: 10.1097/TP.0000000000001292.

UCP2 Expression Is Increased in Pancreas From Brain-Dead Donors and Involved in Cytokine-Induced β Cells Apoptosis.

Author information

1
1 Endocrine Division, Laboratory of Human Pancreatic Islet Biology, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.2 Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.3 ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.

Abstract

BACKGROUND:

Systemic inflammation associated with brain death (BD) decreases islet yield and quality, negatively affecting outcomes of human islet transplantation. A recent study from our group showed an increased expression of uncoupling protein-2 (UCP2) in pancreas from rats with BD as compared with controls. UCP2 is located in the mitochondrial inner membrane and regulates production of reactive oxygen species and glucose-stimulated insulin secretion. It has been suggested that UCP2 also plays a role in β cell apoptosis, but these findings remain controversial.

METHODS:

We have presently performed a case-control study to assess UCP2 expression in pancreas from BD donors (cases) and subjects who underwent pancreatectomy (controls). We next investigated the role of Ucp2 in cytokine-induced apoptosis of rat insulin-producing INS-1E cells.

RESULTS:

UCP2 gene expression was higher in pancreas from BD donors compared with controls (1.73 ± 0.93 vs 0.75 ± 0.66; fold change, P < 0.05). Ucp2 knockdown (80% at the protein and messenger RNA levels) reduced by 30% cytokine-induced apoptosis and nitric oxide production in INS-1E cells. This protection was associated with decreased expression of cleaved (activated) caspases 9 and 3, suggesting that Ucp2 knockdown interferes with cytokine triggering of the intrinsic apoptotic pathway. Moreover, both messenger RNA and protein concentrations of the antiapoptotic protein Bcl-2 were increased after Ucp2 knockdown in INS-1E cells.

CONCLUSIONS:

These data suggest that UCP2 has an apoptotic effect in β cells via regulation of the intrinsic pathway of apoptosis.

PMID:
28222054
DOI:
10.1097/TP.0000000000001292
[Indexed for MEDLINE]

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