Reduction of acute photodamage in skin by topical application of a novel PARP inhibitor

Beatrix Farkas, Marta Magyarlaki, Bela Csete, J. Németh, Gyorgy Rabloczky, Sandor Bernath, Peter Literáti Nagy, B. Sümegi

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The ultraviolet (UV) components of sunlight induce damage to the DNA in skin cells, which is considered to be the initiating step in the harmful biological effects of UV radiation. Repair of DNA damage results in the formation of single-strand DNA breaks, which activate the nuclear poly(ADP-ribose) polymerase (PARP). Overactivation of PARP worsens the oxidative cell damage and impairs the energy metabolism, raising the possibility that moderation of PARP activation following DNA damage may protect skin cells from UV radiation. The topical effects of the novel PARP inhibitor O-(3-pyperidino-2-hydroxy-1-propyl) pyridine-3-carboxylic acid amidoxime monohydrochloride (BGP-15M) were investigated on UV-induced skin damage in a hairless mouse model. For evaluation of the UV-induced acute photodamage to the skin and the potential protective effect of BGP-15M, DNA injury was detected by measuring the formation of single-strand DNA breaks and counting the resulting sunburn (apoptotic) cells. The ADP-ribosylation of PARP was assessed by Western blot analysis and then quantified. In addition, the UV-induced immunosuppression was investigated by the immunostaining of tumor necrosis factor alpha and interleukin-10 expressions in epidermal cells. The signs of inflammation were examined clinically and histochemically. Besides its primary effect in decreasing the activity of nuclear PARP, topically applied BGP-15M proved to be protective against solar and artificial UV radiation-induced acute skin damage. The DNA injury was decreased (P

Original languageEnglish
Pages (from-to)921-932
Number of pages12
JournalBiochemical Pharmacology
Volume63
Issue number5
DOIs
Publication statusPublished - Mar 1 2002

Fingerprint

Poly(ADP-ribose) Polymerases
DNA Damage
Skin
DNA
Single-Stranded DNA Breaks
Ultraviolet radiation
Radiation
Sunburn
Hairless Mouse
Sunlight
Radiation Effects
Carboxylic Acids
Interleukin-10
Adenosine Diphosphate
Immunosuppression
Energy Metabolism
Tumor Necrosis Factor-alpha
Western Blotting
Poly(ADP-ribose) Polymerase Inhibitors
Inflammation

Keywords

  • DNA damage
  • Immunosuppression
  • PARP-inhibitor
  • Photodamage
  • Photoprotection
  • Poly-ADP-ribosylation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Reduction of acute photodamage in skin by topical application of a novel PARP inhibitor. / Farkas, Beatrix; Magyarlaki, Marta; Csete, Bela; Németh, J.; Rabloczky, Gyorgy; Bernath, Sandor; Literáti Nagy, Peter; Sümegi, B.

In: Biochemical Pharmacology, Vol. 63, No. 5, 01.03.2002, p. 921-932.

Research output: Contribution to journalArticle

Farkas, B, Magyarlaki, M, Csete, B, Németh, J, Rabloczky, G, Bernath, S, Literáti Nagy, P & Sümegi, B 2002, 'Reduction of acute photodamage in skin by topical application of a novel PARP inhibitor', Biochemical Pharmacology, vol. 63, no. 5, pp. 921-932. https://doi.org/10.1016/S0006-2952(01)00929-7
Farkas, Beatrix ; Magyarlaki, Marta ; Csete, Bela ; Németh, J. ; Rabloczky, Gyorgy ; Bernath, Sandor ; Literáti Nagy, Peter ; Sümegi, B. / Reduction of acute photodamage in skin by topical application of a novel PARP inhibitor. In: Biochemical Pharmacology. 2002 ; Vol. 63, No. 5. pp. 921-932.
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