Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin

László Virág, Éva Szabó, Edina Bakondi, Péter Bai, Pál Gergely, János Hunyadi, Csaba Szabo

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)189-202
Number of pages14
JournalExperimental Dermatology
Volume11
Issue number3
DOIs
StatePublished - Jun 2002
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Poly(ADP-ribose) Polymerases
Skin
Nitric Oxide
Skin Diseases
Enzyme sensors
Dermatitis
Sunburn
Allergic Contact Dermatitis
Irritants
Contact Dermatitis
Wounds and Injuries
Pathology
Cell death
Erythema
Ultraviolet Rays
Infection Control
Psoriasis
Oxidants
Superoxides

Keywords

  • Inflammation
  • Keratinocyte
  • Nitric oxide
  • Peroxynitrite
  • Poly(ADP-ribose) polymerase
  • Skin

ASJC Scopus subject areas

  • Dermatology

Cite this

Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin. / Virág, László; Szabó, Éva; Bakondi, Edina; Bai, Péter; Gergely, Pál; Hunyadi, János; Szabo, Csaba.

In: Experimental Dermatology, Vol. 11, No. 3, 06.2002, p. 189-202.

Research output: Contribution to journalArticle

Virág, L, Szabó, É, Bakondi, E, Bai, P, Gergely, P, Hunyadi, J & Szabo, C 2002, 'Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin', Experimental Dermatology, vol. 11, no. 3, pp. 189-202. https://doi.org/10.1034/j.1600-0625.2002.110301.x
Virág, László ; Szabó, Éva ; Bakondi, Edina ; Bai, Péter ; Gergely, Pál ; Hunyadi, János ; Szabo, Csaba. / Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin. In: Experimental Dermatology. 2002 ; Vol. 11, No. 3. pp. 189-202.
@article{deff6303329f4e54ad259df4d7d2b435,
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.",
keywords = "Inflammation, Keratinocyte, Nitric oxide, Peroxynitrite, Poly(ADP-ribose) polymerase, Skin",
author = "L{\'a}szl{\'o} Vir{\'a}g and {\'E}va Szab{\'o} and Edina Bakondi and P{\'e}ter Bai and P{\'a}l Gergely and J{\'a}nos Hunyadi and Csaba Szabo",
year = "2002",
month = "6",
doi = "10.1034/j.1600-0625.2002.110301.x",
language = "English (US)",
volume = "11",
pages = "189--202",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin

AU - Virág, László

AU - Szabó, Éva

AU - Bakondi, Edina

AU - Bai, Péter

AU - Gergely, Pál

AU - Hunyadi, János

AU - Szabo, Csaba

PY - 2002/6

Y1 - 2002/6

N2 - 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.

AB - 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.

KW - Inflammation

KW - Keratinocyte

KW - Nitric oxide

KW - Peroxynitrite

KW - Poly(ADP-ribose) polymerase

KW - Skin

UR - http://www.scopus.com/inward/record.url?scp=0036616978&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036616978&partnerID=8YFLogxK

U2 - 10.1034/j.1600-0625.2002.110301.x

DO - 10.1034/j.1600-0625.2002.110301.x

M3 - Article

VL - 11

SP - 189

EP - 202

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

IS - 3

ER -