l-Arginine supplementation induces glutathione synthesis in interscapular brown adipose tissue through activation of glutamate-cysteine ligase expression: The role of nitric oxide

We examined whether nitric oxide (NO) in vivo could induce interscapular brown adipose tissue (IBAT) glutathione synthesis. Data show that NO induces in vivo IBAT glutathione synthesis through activation of glutamate-cysteine ligase (GCL) mRNA and protein expression. This NO effect appeared to be mediated by nuclear factor-κB (NF-κB) activation. We have also observed a complex series of in vivo cellular responses during chronic inhibition of NO synthesis, suggesting that regulatory pathways unrelated to GCL alteration underlie glutathione level increase induced by Nω-nitro-l-arginine methyl ester (l-NAME). In general, glutathione synthesis in IBAT seemed to be finely tuned by NO to provide glutathione for either mediating the effects of NO, or for preventing potential nitrosative stress.