| Theme | Gastrointestinal Diseases and NO | |
|---|---|---|
| Title | Factors that Modulate Biological Activities of Nitric Oxide | |
| Publish Date | 1999/06 | |
| Author | Ryoji Fukushima | Second Department of Surgery, Teikyo University School of Medicine |
| Author | Kota Okinaga | Second Department of Surgery, Teikyo University School of Medicine |
| [ Summary ] | Nitric oxide (NO) production is regulated by three establishedisoforms of nitric oxide synthase(NOS I-III). Whereas NOS II is a transcriptionally regulated enzyme, NOS I and NOS III are considered constitutively expressed proteins. However, evidence generated in recent years indicates that these two isoforms are also subject to expressional regulation. NOS II is generally upregulated by endotoxins, INF gamma, IL1 beta and TNF alpha and downregulated by glucocorticoids as well as cytokines such as members of the transforming growth factor (TGF) family. In contrast, NOS I and NOS III are generally upregulated by sex hormones and downregulated by LPS, INF gamma or TNF alpha. An endogeneousinhibitor of NOS (ADMA or PIN) has been identified which may regulate NO production in vivo. Nitric oxide reacts rapidly with 02- to form ONOO-. It is now considered that ONOO- mediates the toxic action of NO and superoxide anions. Nitration of tyrosine and of tyrosyl residues in proteins may be an important mechanism of derangement of biochemical signal transduction by this compound. Nitric oxide is removed within seconds by its reaction with hemoglobin. The homeostasis of NO in the blood is maintained by a delicate balance between its production by NOSs and its nearly instant scavenging by hemoglobin. Recent evidence suggests that the allosteric and electronic properties of hemoglobin can help them to serve as effective NO carriers. | |