Nitric oxide signaling depends on biotin in Jurkat human lymphoma cells.
Biotin affects gene expression through a diverse array of cell signaling pathways. Previous studies provided evidence that cGMP-dependent signaling also depends on biotin, but the mechanistic sequence of cGMP regulation by biotin is unknown. Here we tested the hypothesis that the effects of biotin in cGMP-dependent cell signaling are mediated by nitric oxide (NO). Human lymphoid (Jurkat) cells were cultured in media containing deficient (0.025 nmol/L), physiological (0.25 nmol/L), and pharmacological (10 nmol/L) concentrations of biotin for 5 wk. 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 the NO synthase (NOS) inhibitor N-monomethyl-arginine. Biotin-dependent production of NO was linked with biotin-dependent expression of endothelial and neuronal NOS, but not inducible NOS. 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 protein kinase G activity. Collectively, the results of this study are consistent with the hypothesis that biotin-dependent cGMP signaling in human lymphoid cells is mediated by NO.
Rodriguez-Melendez
Rocio
R
Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE 68583, USA.
Zempleni
Janos
J
D001710:Biotin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019735:Carbon-Carbon Ligases / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019169:Jurkat Cells; D008223:Lymphoma / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D003470:Culture Media; D009569:Nitric Oxide; D001710:Biotin; D019735:Carbon-Carbon Ligases