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Endogenous nitric oxide induced by interleukin‐1β in rat islets of Langerhans and HIT‐T15 cells causes significant DNA damage as measured by the ‘comet’ assay
Author(s) -
Delaney C.A.,
Green M.H.L.,
Lowe J.E.,
Green I.C.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80673-i
Subject(s) - nitric oxide , peroxynitrite , nitric oxide synthase , dna damage , superoxide dismutase , superoxide , chemistry , comet assay , microbiology and biotechnology , beta cell , biochemistry , islet , biology , endocrinology , dna , oxidative stress , insulin , enzyme , organic chemistry
We have used the comet assay (single cell gel electrophoresis) to measure nitric oxide‐induced DNA damage in rat islets of Langerhans and insulin‐containing HIT‐T15 cells. Damage was induced following treatment with the nitric oxide donor SIN‐1, which also releases Superoxide, but was not reduced by exogenous Superoxide dismutase, suggesting that nitric oxide itself, rather than Superoxide or peroxynitrite may be the active species. The DNA damaging effect of nitric oxide was easily detectable at the earliest time point tested (15 min). Damage also resulted following induction of nitric oxide synthase by the cytokine interleukin‐1β in both islets and HIT‐T15 cells and was prevented by replacing the substrate, arginine, with nitromonomethyl arginine. Thus intracellular levels of nitric oxide generated by interleukin‐1β‐induced nitric oxide synthase were sufficient to cause DNA damage in islet cells and HIT‐T15 cells.