Involvement of the cGMP signalling pathway in the regulation of viability in insulin‐secreting BRIN‐BD11 cells

FEBS Letters

Gao, Hongwei²  Morgan, Noel G¹  Kaminski, Anna¹ 

[1] Endocrine Pharmacology Group, Institute of Biomedical and Clinical Science, Peninsula Medical School, Room N32, ITTC Building, Tamar Science Park, Plymouth, Devon PL6 8BX, UK;Department of Endocrinology, Peking University Third Hospital, Beijing, PR China

关键词: Diabetes;    Apoptosis;    cGMP-dependent kinase;    Islets of Langerhans;    YC-1;    Guanylyl cyclase;   

DOI  :  10.1016/S0014-5793(04)00048-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown