Bryan Nathan S, Fernandez Bernadette O, Bauer Selena M, Garcia-Saura Maria Francisca, Milsom Alexandra B, Rassaf Tienush, Maloney Ronald E, Bharti Ajit, Rodriguez Juan, Feelisch Martin
Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Nat Chem Biol. 2005 Oct;1(5):290-7. doi: 10.1038/nchembio734. Epub 2005 Sep 18.
Mammalian tissues produce nitric oxide (NO) to modify proteins at heme and sulfhydryl sites, thereby regulating vital cell functions. The majority of NO produced is widely assumed to be neutralized into supposedly inert oxidation products including nitrite (NO2(-)). Here we show that nitrite, also ubiquitous in dietary sources, is remarkably efficient at modifying the same protein sites, and that physiological nitrite concentrations account for the basal levels of these modifications in vivo. We further find that nitrite readily affects cyclic GMP production, cytochrome P450 activities, and heat shock protein 70 and heme oxygenase-1 expression in a variety of tissues. These cellular activities of nitrite, combined with its stability and abundance in vivo, suggest that this anion has a distinct and important signaling role in mammalian biology, perhaps by serving as an endocrine messenger and synchronizing agent. Thus, nitrite homeostasis may be of great importance to NO biology.
哺乳动物组织会产生一氧化氮（NO），以修饰血红素和巯基位点处的蛋白质，从而调节重要的细胞功能。人们普遍认为，产生的大部分NO会被中和为假定无活性的氧化产物，包括亚硝酸盐（NO2(-)）。在此，我们表明，同样在饮食来源中普遍存在的亚硝酸盐，在修饰相同蛋白质位点方面非常高效，并且生理浓度的亚硝酸盐可解释体内这些修饰的基础水平。我们进一步发现，亚硝酸盐能轻易影响多种组织中环鸟苷酸的产生、细胞色素P450的活性以及热休克蛋白70和血红素加氧酶-1的表达。亚硝酸盐的这些细胞活性，再加上其在体内的稳定性和丰富性，表明这种阴离子在哺乳动物生物学中具有独特而重要的信号传导作用，或许是通过充当内分泌信使和同步剂来实现的。因此，亚硝酸盐稳态可能对NO生物学极为重要。
