Nitric oxide signaling depends on biotin in Jurkat human lymphoma cells

Biotin affects gene expression through various signaling pathways. Previous studies suggest that cGMP‐dependent signaling also depends on biotin, but the mechanism of cGMP regulation is unknown. Here we tested the hypothesis that effects of biotin in cGMP‐dependent cell signaling are mediated by nitric oxide (NO). Human lymphoid (Jurkat) cells were cultured in media containing deficient, physiological, and pharmacological concentrations of biotin. Both levels of intracellular biotin and NO exhibited a dose‐dependent relationship in regard to biotin concentrations in culture media. Effects of biotin on NO levels were disrupted by both the NO synthase (NOS) inhibitors and NO donors. Biotin‐dependent production of NO was linked with biotin‐dependent expression of endothelial and neuronal NOS, but not the inducible iNOS. Previous studies revealed that NO is an activator of guanylate cyclase. Consistent with these previous observations, biotin‐dependent generation of NO increased the abundance of cGMP in Jurkat cells. Finally, the biotin‐dependent generation of cGMP increased the activity of protein kinase G. Collectively this study is consistent with the hypothesis that biotin‐dependent cGMP signaling in human lymphoid cells is mediated by NO. (Supported by UNL ARD Hatch Act funds, NIH DK063945, DK077816 and ES015206, USDA CSREES 2006‐35200‐17138, and NSF EPSCoR EPS‐0701892.)

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