Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0849640 (skin damage)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genotoxic stress triggers the p53 tumor suppressor network to activate cellular responses that lead to cell cycle arrest, DNA repair, apoptosis or senescence. This network functions mainly through transactivation of different downstream targets, including cell cycle inhibitor p21, which is required for short-term cell cycle arrest or long-term cellular senescence, or proapoptotic genes such as p53 upregulated modulator of apoptosis (PUMA) and Noxa. However, the mechanism that switches from cell cycle arrest to apoptosis is still unknown. In this study, we found that mice harboring a hypomorphic mutant p53, R172P, a mutation that abrogates p53-mediated apoptosis while keeping cell cycle control mostly intact, are more susceptible to ultraviolet-B (UVB)-induced skin damage, inflammation and immunosuppression than wild-type mice. p53(R172P) embryonic fibroblasts (MEFs) are hypersensitive to UVB and prematurely senesce after UVB exposure, in stark contrast to wild-type MEFs, which undergo apoptosis. However, these mutant cells are able to repair UV-induced DNA lesions, indicating that the UV hypersensitive phenotype results from the subsequent damage response. Mutant MEFs show an induction of p53 and p21 after UVR, while wild-type MEFs additionally induce PUMA and Noxa. Importantly, p53(R172P) MEFs failed to downregulate anti-apoptotic protein Bcl-2, which has been shown to play an important role in p53-dependent apoptosis. Taken together, these data demonstrate that in the absence of p53-mediated apoptosis, cells undergo cellular senescence to prevent genomic instability. Our results also indicate that p53-dependent apoptosis may play an active role in balancing cellular growth.
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PMID:Absence of p53-dependent apoptosis leads to UV radiation hypersensitivity, enhanced immunosuppression and cellular senescence. 2070 98

To investigate the protective effect of ethanol extract of Gynura bicolor (GB) against UVB-induced photodamage of skin and the possible mechanisms. DPPH (1,1-diphenyl-2-pico radical) test was used to detect the antioxidant capacity of ethanol extract of Gynura bicolor (GB). The protective effects of GB against UVB irritation were detected both in Hacat cells and photodamage rat models. UVB irradiation could inhibit viability and induce apoptosis of Hacat cells in a dose-dependent manner. The pretreatment of Hacat cells by GB could obviously reverse the effects in a dose-dependent manner. The mRNA and protein expressions of p53, Bax, caspase-3 were increased, while anti-apoptotic protein Bcl-2 was decreased and this effect could be reversed by GB pretreatment in a dose-dependent manner. In vivo, the application of GB could alleviate the skin damage of SD rats and improve the superficial inflammation of the dermis as well as inhibit the expressions of P53 and Caspase-3 induced by UVB irradiation. Ethanol extract of Gynura bicolor could protect the photodamage of human Hacat keratinocytes and SD rats against UVB irradiation by inhibiting P53-mediated Bcl-2/ BAX/Casaspe-3 apoptosis pathway.
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PMID:Ethanol extract of Gynura bicolor (GB) protects against UVB-induced photodamage of skin by inhibiting P53-mediated Bcl-2/BAX/Caspase-3 apoptosis pathway. 3153 24