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

Farkas, Beatrix; Magyarlaki, Marta; Csete, B; Németh, József; Rablóczky, G.; Bernáth, Sándor; Nagy, Péter; Sümegi, Balázs

doi:10.1016/s0006-2952(01)00929-7

Cited by 43 publications

(35 citation statements)

References 65 publications

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“…35 UV-induced acute photodamage in mouse skin could be reduced by topical application of a novel PARP inhibitor (BGP-15M) that was shown to decrease the number of single-strand DNA breaks and to downregulate IL-10 and TNF␣-levels in epidermal cells. 48 Finally, in a murine model of allergen-induced asthma, 3-AB prevented airway inflammation elicited by ovalbumin. Likewise, Adprt knockout mice were resistant to ovalbumin-induced inflammation.…”

Section: Ischaemia-reperfusion Damage In Brain Heart Liver Kidneymentioning

confidence: 97%

Poly(ADP‐ribosyl)ation inhibitors: Promising drug candidates for a wide variety of pathophysiologic conditions

Beneke

Diefenbach

Bürkle

2004

Intl Journal of Cancer

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Poly(ADP-ribose) polymerases are involved in many aspects of regulation of cellular functions. Using NAD ؉ as a substrate, they catalyse the covalent transfer of ADP-ribose units onto several acceptor proteins to form a branched ADP-ribose polymer. The best characterised and first discovered member of this multiprotein family is PARP-1. Its catalytic activity is markedly stimulated upon binding to DNA strand interruptions, and the resulting polymer is thought to function in chromatin relaxation as well as in signalling the presence of damage to DNA repair complexes and in regulating enzyme activities. Moderate activation of PARP-1 facilitates the efficient repair of DNA damage arising from monofunctional alkylating agents, reactive oxygen species or ionising radiation, but severe genotoxic stress leads to rapid energy consumption and subsequently to necrotic cell death. The latter aspect of PARP-1 activity has been implicated in the pathogenesis of various clinical conditions such as shock, ischaemia-reperfusion and diabetes. Inhibition of ADP-ribose polymer formation has been shown to be effective, on the one hand, in the treatment of cancer in combination with alkylating agents by suppressing DNA repair and thus driving tumour cells into apoptosis, and on the other hand it appears to be a promising drug target for the treatment of pathologic conditions involving oxidative stress. In view of the existence of several members of the PARP family in mammalian cells, one has to be aware of possible side effects but also of a wide spectrum of potential clinical applications, which calls for the development of more specific inhibitors. © 2004 Wiley-Liss, Inc. Key words: DNA damage; PARP; cancer chemotherapy; radiotherapy; ischaemia-reperfusion damage; diabetes; shock; Parkinson syndromePoly(ADP-ribosyl)ation is a posttranslational modification of proteins in eukaryotic cells performed by a family of NAD ϩ ADP-ribosyl transferases, the poly(ADP-ribose) polymerases (PARPs). NAD ϩ molecules as precursor are cleaved into nicotinamide and ADP-ribose moieties, and the latter are covalently attached to glutamic or aspartic acid residues of proteins, with PARP itself being the major acceptor. Poly(ADP-ribosyl)ation may alter the activity of acceptor protein, leading to inactivation due to the attachment of a highly complex, branched polymer carrying large numbers of negative charges (Fig. 1). The polymer is rapidly degraded by the enzyme poly(ADP-ribose) glycohydrolase (PARG), limiting the half-life of the polymer to approximately 1 min under conditions of DNA breakage. Poly(ADPribosyl)ation was originally discovered as an immediate response of cells to DNA strand-break-inducing agents, i.e., ionising radiation, alkylating agents and oxidants. Polymer formation in living cells after genotoxic stresses is mainly dependent on PARP-1 (encoded by the ADPRT gene), the first-discovered and best-investigated member of the PARP family. After binding of PARP-1 with its 2 zinc-fingers within the N-terminal DNA-binding domain to double...

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Section: Ischaemia-reperfusion Damage In Brain Heart Liver Kidneymentioning

confidence: 97%

Poly(ADP‐ribosyl)ation inhibitors: Promising drug candidates for a wide variety of pathophysiologic conditions

Beneke

Diefenbach

Bürkle

2004

Intl Journal of Cancer

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“…UVB-induced oxidant is the cause of the second peak of PARP activation It has been suggested earlier that oxidative DNA damage induced by UVB is the most probable cause of PARP activation in UVB-irradiated cells (Caldecott, 2003b;Chang et al, 2002;Farkas et al, 2002). Therefore, we examined whether both the phases of PARP activation were due to a UVBinduced oxidant (Fig.…”

Section: Biphasic Activation Of Parp In Response To Uvbmentioning

confidence: 98%

“…Indeed, a recent study has shown that PARP inhibition significantly delays removal of UVB-induced CPD (Flohr et al, 2003). Finally, PARP activation has been linked to UVB-induced apoptosis in cultured cells or in mouse skin (Chang et al, 2002;Farkas et al, 2002;Mi et al, 2003).…”

mentioning

confidence: 99%

“…Most of the UVC-induced DNA damage is direct lesions, such as CPD, which are repaired by NER, and it is not known if strand breaks generated during NER are exposed and available for PARP activation. Recent studies reporting UVB-induced PARP activation in skin (Farkas et al, 2002) and keratinocytes (Chang et al, 2002) suggested that oxidative DNA damage is the cause of PARP activation, although it was not experimentally determined. Therefore, we examined mechanism of early PARP activation in mouse embryonic fibroblasts exposed to UVB and UVC radiation.…”

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confidence: 99%

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Mechanism of early biphasic activation of poly(ADP-ribose) polymerase-1 in response to ultraviolet B radiation

Vodenicharov

Ghodgaonkar

Halappanavar

et al. 2005

Journal of Cell Science

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The damage to DNA caused by ultraviolet B radiation (280-320 nm) contributes significantly to development of sunlight-induced skin cancers. The susceptibility of mice to ultraviolet B-induced skin carcinogenesis is increased by an inhibitor of the DNA damage-activated nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP), hence PARP activation is likely to be associated with cellular responses that suppress carcinogenesis. To understand the role of activated PARP in these cellular functions, we need to first clearly identify the cause of PARP activation in ultraviolet B-irradiated cells. Ultraviolet B, like ultraviolet C, causes direct DNA damage of cyclobutane pyrimidine dimer and 6, 4-photoproduct types, which are subjected to the nucleotide excision repair. Moreover, ultraviolet B also causes oxidative DNA damage, which is subjected to base excision repair. To identify which of these two types of DNA damage activates PARP, we examined mechanism of early PARP activation in mouse fibroblasts exposed to ultraviolet B and C radiations. The ultraviolet B-irradiated cells rapidly activated PARP in two distinct phases, initially within the first 5 minutes and later between 60-120 minutes, whereas ultraviolet C-irradiated cells showed only the immediate PARP activation. Using antioxidants, local irradiation, chromatin immunoprecipitation and in vitro PARP assays, we identified that ultraviolet radiation-induced direct DNA damage, such as thymine dimers, cause the initial PARP activation, whereas ultraviolet B-induced oxidative damage cause the second PARP activation. Our results suggest that cells can selectively activate PARP for participation in different cellular responses associated with different DNA lesions.

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“…It's changes in the dermal elastic fibers attributed to a loss of linearity and curling (Imokawa et al, 1995). UV irradiation-induced injury to the skin can be photodamage (Farkas et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Anti-Wrinkle Effect of Ulmus davidiana Extracts

Kim¹,

Seo²,

Lee³

et al. 2011

Korean Journal of Medicinal Crop Science

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: The bark of the root and stem of Ulmus davidiana var. japonica has been used as a traditional Korean medicine to treat inflammatory disorders. This plant reportedly shows antioxidant, anticancer, and anti-inflammatory effects. In this study, we investigated the protective effects of Ulmus davidiana var. japonica ethanolic extract (UDE) on UVB irradiation-induced wrinkle in hairless mice. We evaluated for their free radical-scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the anti-elastase activities, and for their anti-matrix metalloproteinase-1 (MMP-1) activity in human skin fibroblast cells. In the wrinkle measurement and image analysis of skin replicas, the results showed that UDE significantly inhibited wrinkle formation caused by chronic UVB irradiation. These results suggest that UDE has anti-wrinkle activity.

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

Cited by 43 publications

References 65 publications

Poly(ADP‐ribosyl)ation inhibitors: Promising drug candidates for a wide variety of pathophysiologic conditions

Poly(ADP‐ribosyl)ation inhibitors: Promising drug candidates for a wide variety of pathophysiologic conditions

Mechanism of early biphasic activation of poly(ADP-ribose) polymerase-1 in response to ultraviolet B radiation

Anti-Wrinkle Effect of Ulmus davidiana Extracts

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