title: Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin.
abstract: In the last decade it has become well established that in the skin, nitric oxide (NO), a diffusable gas, mediates various physiologic functions ranging from the regulation of cutaneous blood flow to melanogenesis. If produced in excess, NO combines with superoxide anion to form peroxynitrite (ONOO-), a cytotoxic oxidant that has been made responsible for tissue injury during shock, inflammation and ischemia-reperfusion. The opposite effects of NO and ONOO- on various cellular processes may explain the 'double-edged sword' nature of NO depending on whether or not cellular conditions favour peroxynitrite formation. Peroxynitrite has been shown to activate the nuclear nick sensor enzyme, poly(ADP-ribose) polymerase (PARP). Overactivation of PARP depletes the cellular stores of NAD+, the substrate of PARP, and the ensuing 'cellular energetic catastrophy' results in necrotic cell death. Whereas the role of NO in numerous skin diseases including wound healing, burn injury, psoriasis, irritant and allergic contact dermatitis, ultraviolet (UV) light-induced sunburn erythema and the control of skin infections has been extensively documented, the intracutaneous role of peroxynitrite and PARP has not been fully explored. We have recently demonstrated peroxynitrite production, DNA breakage and PARP activation in a murine model of contact hypersensitivity, and propose that the peroxynitrite-PARP route represents a common pathway in the pathomechanism of inflammatory skin diseases. Here we briefly review the role of NO in skin pathology and focus on the possible roles played by peroxynitrite and PARP in various skin diseases.
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. viraglaszlo@hotmail.com
authors.forename: László
authors.initials: L
authors.lastname: Virág
authors.forename: Eva
authors.initials: E
authors.lastname: Szabó
authors.forename: Edina
authors.initials: E
authors.lastname: Bakondi
authors.forename: Péter
authors.initials: P
authors.lastname: Bai
authors.forename: Pál
authors.initials: P
authors.lastname: Gergely
authors.forename: János
authors.initials: J
authors.lastname: Hunyadi
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
mesh_terms: D000818:Animals; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D016877:Oxidants / Q000633:toxicity; D030421:Peroxynitrous Acid / Q000502:physiology*; D011064:Poly Adenosine Diphosphate Ribose / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012867:Skin / Q000201:enzymology; D012879:Skin Physiological Phenomena
chemical_list: D016877:Oxidants; D030421:Peroxynitrous Acid; D011064:Poly Adenosine Diphosphate Ribose; D009569:Nitric Oxide; D011065:Poly(ADP-ribose) Polymerases