Reactive nitrogen species

Reactive nitrogen species (Engl. Reactive nitrogen species , RNS) is the name given to highly reactive nitrogen compounds . They play an important role in a number of physiological , but also pathophysiological processes. Analogous to the reactive oxygen species that cause oxidative stress , reactive nitrogen species cause nitrosative stress . The reactive nitrogen species are responsible for some cell pathological phenomena that were previously only attributed to the reactive oxygen species. Nitric oxide and its secondary product peroxynitrite are counted among the reactive nitrogen species.

Emergence

The relatively stable radical nitrogen monoxide (NO ^· ) is created in the cells by the catalytic effect of NO synthases (NOS). While responding L arginine with molecular oxygen to form nitric oxide and L -citrulline . The nitrogen monoxide formed diffuses to the cell membrane.

The also radical hyperoxide anion (O ₂ ^{· -} ) is formed on the cell membrane with the help of the enzyme NADPH oxidase (NOX) . In a diffusion-limited reaction, the nitrogen monoxide reacts with the hyperoxide anion to form the non-radical but highly reactive peroxynitrite :

NO ^· + O ₂ ^{· -} → ONOO ^-

Because of its high redox potential, peroxynitrite is much more aggressive than its two precursor molecules.

Peroxynitrite reacts with the always present carbon dioxide to form the short-lived nitrosoperoxycarbonate ion, which breaks down into two highly reactive radicals that are responsible for the DNA damage of peroxynitrite:

ONOO ^- + CO ₂ → ONOOCOO ^- → NO ₂ ^* + CO ₃ ^{- ·}

In addition to animal cells, plant cells also produce nitric oxide and thus potentially reactive nitrogen species.

Effects

The reactive nitrogen species are important for a variety of physiological processes, including vascular tone and the immune response. The main mechanism is the induction of apoptosis (programmed cell death). Peroxynitrite is able to lower the glutathione level intracellularly and thereby bring about apoptosis.

Nitrosative stress induced by reactive nitrogen species is believed to be involved in a number of neurological, inflammatory , metabolic, and cardiovascular diseases .

proof

A marker of nitrosative stress is nitrotyrosine . It is formed during the reaction of tyrosine with reaction products of the nitrogen species and can be detected in vitro using suitable methods.

further reading

• A. Hausladen et al: Nitrosative Stress: Activation of the Transcription Factor OxyR. In: Cell 86, 1996, pp. 719-729, doi : 10.1016 / S0092-8674 (00) 80147-6
• A. Hausladen et al: Nitrosative stress: Metabolic pathway involving the flavohemoglobin. In: PNAS 95, 1998, pp. 14100-14105. (PDF; 202 kB)
• B. Maintenance: Different protective mechanisms of human tumor cells against apoptosis induction by reactive oxygen and nitrogen species. Dissertation (PDF; 6.03 MB), Albert-Ludwigs-University Freiburg im Breisgau, 2006

Individual evidence

1. ↑ GL Squadrito and WA Pryor: Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite and carbon dioxide. In: Free Radical Biol Chem 25, 1998, pp. 392-403, PMID 9741578 .
2. ^ R. Loch: Antimicrobial agents as potential anti-tumor agents , dissertation, Albert-Ludwigs-Universität Freiburg i. Br., 2007, p. 7.
3. ↑ N. Pauly et al .: Reactive oxygen and nitrogen species and glutathione: key players in the legume-Rhizobium symbiosis. In: Journal of Experimental Botany 57, 2006, pp. 1769-1776. doi : 10.1093 / jxb / erj184 PMID 16698817
4. ^ G. Bauer: Reactive Oxygen and Nitrogen Species: Efficient, Selective, and Interactive Signals During Intercellular Induction of Apoptosis. In: Anticancer Res 20, 2000, pp. 4115-4140, PMID 11205238 .
5. ^ G. Bauer et al.: Reactive oxygen species and apoptosis. In: Handbook of Exp. Pharmakology RG Cameron and G. Feuer (editors), Springer Verlag, 142, 2000, pp. 275-318.
6. ↑ B. Zucker et al: Glutathione depletion in fibroblasts is the basis for apoptosis induction by endogenous reactive oxygen species. In: Cell Death Differ 4, 1997, pp. 388-395, PMID 16465257 .
7. ↑ R. Radi et al.: Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. In: Arch Biochem Biophys 288, 1991, pp. 481-487, PMID 1654835 .
8. ↑ RM Uppu et al: Cardiovascular effects of peroxynitrite. In: Clin Exp Pharmacol Physiol 34, 2007, pp. 933-937, PMID 17645643 .
9. ↑ R. Radi et al: Unraveling peroxynitrite formation in biological systems. In: Free Radic Biol Med 30, 2001, pp. 463-488, PMID 11182518 .

Web links

• Nitrosative Stress ( Memento from September 22, 2010 in the Internet Archive ) Specialist brochure