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Inducible nitric oxide synthase-nitric oxide plays an important role in acute and severe hypoxic injury to pancreatic beta cells

Title
Inducible nitric oxide synthase-nitric oxide plays an important role in acute and severe hypoxic injury to pancreatic beta cells
Authors
Ko S.-H.Ryu G.R.Kim S.Ahn Y.-B.Yoon K.-H.Kaneto H.Ha H.Kim Y.S.Song K.-H.
Ewha Authors
하헌주
SCOPUS Author ID
하헌주scopus
Issue Date
2008
Journal Title
Transplantation
ISSN
0041-1337JCR Link
Citation
vol. 85, no. 3, pp. 323 - 330
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
BACKGROUND. Islet transplantation is a potential strategy to cure type 1 diabetes mellitus. However, a substantial part of the islet graft becomes nonfunctional due to several factors including hypoxia. However, the precise mechanism of cell damage is largely unknown in hypoxic exposure to pancreatic beta cells. The aim of the present study was to investigate whether acute and severe hypoxic injury could involve inducible nitric oxide synthase (iNOS)-nitric oxide (NO) signaling in beta cells. METHODS. The rat beta cell line (INS-1) and primary rat islets were incubated in an anoxic chamber. Cell viability was determined by propium iodide staining or cell counting kit. The expression of iNOS mRNA and protein was examined using reverse-transcription polymerase chain reaction and Western blot analysis. NO production was measured as nitrite accumulation by Griess reagent method. RESULTS. After hypoxic exposure, marked cell death occurred in INS-1 cells and rat islets, accompanied by increase in activated caspase-3 expression. NO production was increased in the culture medium in a time-dependent manner. Increase in expression of iNOS mRNA and protein was found. Pretreatment with a selective iNOS inhibitor, 1400W, significantly prevented cell death during hypoxia. In addition, hypoxia activated c-Jun N-terminal kinase (JNK) significantly, but the addition of 1400W inhibited hypoxia-induced JNK phosphorylation. CONCLUSIONS. Our data suggest that iNOS-NO plays an important role in acute and severe hypoxic injury to pancreatic beta cells. Therefore, iNOS-NO might be a potential therapeutic target for preserving beta cell survival in islet transplantation through prevention of hypoxia-mediated cell death. © 2008 Lippincott Williams & Wilkins, Inc.
DOI
10.1097/TP.0b013e31816168f9
Appears in Collections:
약학대학 > 약학과 > Journal papers
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