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 language | English |
|---|---|
| Pages (from-to) | 921-932 |
| Number of pages | 12 |
| Journal | Biochemical Pharmacology |
| Volume | 63 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 1 2002 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Reduction of acute photodamage in skin by topical application of a novel PARP inhibitor
AU - Farkas, Beatrix
AU - Magyarlaki, Marta
AU - Csete, Bela
AU - Németh, J.
AU - Rabloczky, Gyorgy
AU - Bernath, Sandor
AU - Literáti Nagy, Peter
AU - Sümegi, B.
PY - 2002/3/1
Y1 - 2002/3/1
N2 - 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
AB - 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
KW - DNA damage
KW - Immunosuppression
KW - PARP-inhibitor
KW - Photodamage
KW - Photoprotection
KW - Poly-ADP-ribosylation
UR - http://www.scopus.com/inward/record.url?scp=0036496950&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036496950&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(01)00929-7
DO - 10.1016/S0006-2952(01)00929-7
M3 - Article
C2 - 11911844
AN - SCOPUS:0036496950
VL - 63
SP - 921
EP - 932
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 5
ER -