Cyclic AMP mediates endothelial protection by nitric oxide

Tobias Polte, Henning Schröder

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Incubation with TNF-α (50 ng/ml) for 72 hours markedly reduced viability of endothelial cells. A 6-hour preincubation with S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 3-100 μM) protected cells in a concentration-dependent manner and decreased TNF-α-mediated toxicity by up to 70%. Cytoprotection by SNAP was completely abolished by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine and mimicked by 8-bromo cyclic AMP or forskolin. SNAP produced significant increases in cyclic GMP and cyclic AMP, both being abrogated in the presence of the NO scavenger 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Moreover, no endothelial protection by SNAP was detected in the presence of the protein kinase A inhibitor KT5720, whereas the protein kinase G inhibitor KT5823 left cytoprotection virtually unaltered. Our results demonstrate a crucial role for cyclic AMP in mediating NO-induced endothelial protection against TNF-α, possibly through cyclic GMP-dependent inhibition of cyclic AMP breakdown. NO-dependent endothelial protection may ultimately result from cyclic AMP-induced up-regulation of antioxidant proteins or down-regulation of cytotoxic processes.

Original languageEnglish (US)
Pages (from-to)460-465
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume251
Issue number2
DOIs
StatePublished - Oct 20 1998

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