Naturally occurring neuronal NO-synthase inactivators found in Nicotiana tabacum (Solanaceae) and other plants.

NO-synthase (NOS) is a heme-containing enzyme that catalyzes the oxidation of L-arginine to nitric oxide, an important cellular signaling molecule. Recently, it was found that aqueous extracts of tobacco cigarettes cause the inactivation of the neuronal isoform of NOS (nNOS) and that this may explain some of the toxicological effects of smoking. Although the exact identity of the chemical inactivator(s) is not known, we wondered if extracts prepared from other plants, including those closely related to tobacco, Nicotiana tabacum (Solanaceae), would similarly inactivate nNOS.

Metabolism-based inactivation of neuronal nitric-oxide synthase by components of cigarette and cigarette smoke.

It has been shown that administration of cigarette smoke to rats leads to loss of neuronal nitric-oxide synthase (nNOS) activity and nNOS protein in penile tissue. The exact mechanism for this loss of activity and protein is not known. In the current study, we investigated whether extracts prepared from cigarette smoke or from the cigarette itself could directly inhibit nNOS activity.

Proteolytic degradation of nitric oxide synthase: effect of inhibitors and role of hsp90-based chaperones.

Nitric oxide synthase (NOS) is a highly regulated enzyme that produces nitric oxide, a critical messenger in many physiological processes. In this perspective, we explore the role of proteolytic degradation of NOS, in particular the inducible and neuronal isoforms of NOS, as a mechanism of regulation of the enzyme. The ubiquitin-proteasome and calpain pathways are the major proteolytic systems identified to date that are responsible for this regulated degradation.