30 April 2015 : Original article
The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT KeratinocytesAijun ChenAE, Xin HuangBD, Zhenan XueCE, Di CaoDE, Kun HuangCE, Jin ChenEF, Yun PanBE, Yongliang GaoAG
Med Sci Monit Basic Res 2015; 21:86-95
BACKGROUND: Skin cancer is the most common cancer in the United States, and ultraviolet B (UVB) radiation-induced DNA damage is the major environmental factor underlying skin cancer development. p21, a p53-inducible protein, plays a key role in the cellular response to UVB-induced DNA damage.
MATERIAL AND METHODS: Through p21 silencing and overexpression, we investigated the role of p21 in apoptosis, proliferation, cell cycle arrest, and oxidative stress in UVB-irradiated HaCaT keratinocytes.
RESULTS: We found that UVB exposure induced significant p21 downregulation (p<0.05) and was associated with significantly increased apoptosis, significantly decreased proliferation, and significantly increased G2 phase arrest (p<0.05) in UVB-irradiated HaCaT keratinocytes. p21 silencing significantly promoted apoptosis, significantly inhibited G2 phase arrest, and significantly inhibited proliferation (p<0.05), but after UVB irradiation, p21 silencing demonstrated a less significant pro-apoptotic effect and a more significant inhibition of G2 phase arrest (p<0.05), which was reflected in significantly higher proliferative activity (p<0.05). p21 overexpression acted in an anti-apoptotic manner in the absence of UVB-induced DNA damage but acted in a pro-apoptotic manner in the presence of UVB-induced DNA damage, displaying an “antagonistic duality” similar to other growth-promoting oncoproteins. p53 expression mirrored p21 expression, suggesting a regulatory feedback mechanism between p21 and p53 expression. p21 overexpression significantly downregulated glutathione peroxidase and superoxide dismutase antioxidant activity (p<0.05) while significantly upregulating hydrogen peroxide and malondialdehyde content (p<0.05), suggesting a role in decreasing antioxidant defense capabilities in UVB-irradiated HaCaT keratinocytes.
CONCLUSIONS: These findings reveal that p21 may play a key role in HaCaT keratinocytes’ response to UVB exposure.
Keywords: Apoptosis - radiation effects, Analysis of Variance, Blotting, Western, Cell Proliferation - radiation effects, Cyclin-Dependent Kinase Inhibitor p21 - metabolism, DNA Damage, DNA Primers - genetics, G2 Phase Cell Cycle Checkpoints - radiation effects, Gene Expression Regulation - radiation effects, Glutathione Peroxidase - metabolism, Hydrogen Peroxide - metabolism, Keratinocytes - radiation effects, Malondialdehyde - metabolism, Oxidative Stress - radiation effects, Real-Time Polymerase Chain Reaction, Superoxide Dismutase - metabolism, Tumor Suppressor Protein p53 - metabolism, Ultraviolet Rays
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