EXOGENOUS, BUT NOT ENDOGENOUS, NITRIC-OXIDE INCREASES PROLIFERATION RATES IN SENESCENT HUMAN FIBROBLASTS

We investigated the effects of endogenously produced and exogenously a pplied nitric oxide (NO) on cell proliferation rates and cell cycle re gulation in senescent human fibroblasts (WI38), Induction of inducible nitric oxide synthase by tumor necrosis factor-alpha, interferon-gamm a and interleukin-1 beta inhibited cell proliferation and led to a G1 arrest. These effects were partially reversible by N-G-monomethyl-argi nine (NMA). Addition of the NO donors sodium nitroprusside (SNP) or S- nitroso-N-acetylpenicillamine (SNAP) increased cell proliferation rate s as well as the S/G2 fraction, This points to a functional role of NO in cell cycle regulation and cell proliferation in human fibroblasts which depends on the mode of NO generation as well as the culture cond itions used. (C) 1997 Federation of European Biochemical Societies.