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

Anna Kaminski; Hongwei Gao; Noel G Morgan

doi:10.1016/S0014-5793(04)00048-1

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

FEBS Lett. 2004 Feb 13;559(1-3):118-24. doi: 10.1016/S0014-5793(04)00048-1.

Authors

Anna Kaminski¹, Hongwei Gao, Noel G Morgan

Affiliation

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.

PMID: 14960318
DOI: 10.1016/S0014-5793(04)00048-1

Abstract

We have evaluated the hypothesis that cGMP may serve as an intracellular messenger regulating the viability of pancreatic beta-cells. A direct activator of soluble guanylyl cyclase, YC-1, caused a time- and dose-dependent loss of viability in clonal BRIN-BD11 beta-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-Ialpha, -Ibeta 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Cell Line
Cell Survival
Cyclic GMP / analogs & derivatives*
Cyclic GMP / pharmacology
Cyclic GMP / physiology*
Cyclic GMP-Dependent Protein Kinase Type I
Cyclic GMP-Dependent Protein Kinase Type II
Cyclic GMP-Dependent Protein Kinases / drug effects
Cyclic GMP-Dependent Protein Kinases / physiology*
Dactinomycin / pharmacology
Guanylate Cyclase / drug effects
Indazoles / pharmacology
Insulin / metabolism
Insulin Secretion
Islets of Langerhans / cytology*
Islets of Langerhans / metabolism
Protein Isoforms / analysis
Rats
Signal Transduction / physiology*
Thionucleotides / pharmacology
Transcription, Genetic

Substances

8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate
Indazoles
Insulin
Protein Isoforms
Thionucleotides
3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
Dactinomycin
Cyclic GMP-Dependent Protein Kinase Type I
Cyclic GMP-Dependent Protein Kinase Type II
Cyclic GMP-Dependent Protein Kinases
PRKG1 protein, human
PRKG2 protein, human
Prkg2 protein, rat
Guanylate Cyclase
Cyclic GMP