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- Title
Involvement of the cGMP signalling pathway in the regulation of viability in insulin-secreting BRIN-BD11 cells
- Authors
Kaminski, Anna; Gao, Hongwei; Morgan, Noel G.
- Abstract
We have evaluated the hypothesis that cGMP may serve as an intracellular messenger regulating the viability of pancreatic β-cells. A direct activator of soluble guanylyl cyclase, YC-1, caused a time- and dose-dependent loss of viability in clonal BRIN-BD11 β-cells. This was accompanied by a rise in cGMP and was antagonised by Rp-8-pCPT-cGMPS, a selective inhibitor of protein kinase G (PKG). Reverse transcription polymerase chain reaction analysis confirmed that BRIN-BD11 cells (and human islets) express all three known isoforms of PKG (PKG-Iα, -Iβ and II). Cell death induced by YC-1 was not sensitive to cell-permeable caspase inhibitors and was not accompanied by oligonucleosomal DNA fragmentation. The response was, however, inhibited by actinomycin D, suggesting that a transcription-dependent pathway of programmed cell death is involved in the actions of cGMP.
- Subjects
GUANYLATE cyclase; PANCREATIC beta cells; PROTEIN kinases; CELLULAR signal transduction
- Publication
FEBS Letters, 2004, Vol 559, Issue 1-3, p118
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/S0014-5793(04)00048-1