PT  - JOURNAL ARTICLE
AU  - Yoichi Osawa
AU  - Ezra R. Lowe
AU  - Andrew C. Everett
AU  - Anwar Y. Dunbar
AU  - Scott S. Billecke
TI  - Proteolytic Degradation of Nitric Oxide Synthase: Effect of Inhibitors and Role of hsp90-Based Chaperones
AID  - 10.1124/jpet.102.035055
DP  - 2003 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 493--497
VI  - 304
IP  - 2
4099  - http://jpet.aspetjournals.org/content/304/2/493.short
4100  - http://jpet.aspetjournals.org/content/304/2/493.full
SO  - J Pharmacol Exp Ther2003 Feb 01; 304
AB  - 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. The degradation of NOS is affected by diverse agents, including glucocorticoids, caveolin, neurotoxic compounds, and certain NOS inhibitors. Some irreversible inactivators of NOS enhance the proteolytic degradation of the enzyme, and this property may be of great importance in understanding the biological effects of these inhibitors, some of which are being developed for clinical use. Analogies with the regulated degradation of liver microsomal cytochromes P450, which are related to NOS, provide a framework for understanding these processes. Finally, a new perspective on the regulation of NOS by hsp90-based chaperones is presented that involves facilitated heme insertion into the enzyme. The American Society for Pharmacology and Experimental Therapeutics