Nitric oxide and superoxide in cultured cells: limited production and influence on DNA synthesis.
The ability of superoxide (O2-) and NO to influence DNA synthesis, as estimated by [3H]thymidine incorporation in logarithmically growing cells, was evaluated in three human cell types: embryonic lung fibroblasts, skin fibroblasts, and mesangial cells. Nontoxic rates of O2- generation (0.2 nM/min-0.2 microM/min) only slightly stimulated DNA synthesis in mesangial cells (10-13% increase) and did not affect fibroblast DNA synthesis. Nontoxic rates of NO generation (0.1-10 microM/min) also had only limited effects, inhibiting DNA synthesis in lung and skin fibroblasts slightly (10-20% decrease) but not affecting mesangial cells. In all three cell types, neither O2- nor NO was generated at high enough endogenous rates to support an autocrinic regulation of DNA synthesis. This and other lines of evidence indicate that a reaction between O2- and NO is unlikely to account for their opposing effects on DNA synthesis.
Firnhaber
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Institut für Physiologische Chemie I, Universität Düsseldorf, Germany.
Murphy
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ME
D002477:Cells / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D005347:Fibroblasts; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism* / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D013481:Superoxides; D009569:Nitric Oxide; D004247:DNA; D013936:Thymidine