The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes

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. MATERI...

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Autores principales: Chen, Aijun, Huang, Xin, Xue, Zhenan, Cao, Di, Huang, Kun, Chen, Jin, Pan, Yun, Gao, Yongliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427023/
https://www.ncbi.nlm.nih.gov/pubmed/25925725
http://dx.doi.org/10.12659/MSMBR.893608
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author Chen, Aijun
Huang, Xin
Xue, Zhenan
Cao, Di
Huang, Kun
Chen, Jin
Pan, Yun
Gao, Yongliang
author_facet Chen, Aijun
Huang, Xin
Xue, Zhenan
Cao, Di
Huang, Kun
Chen, Jin
Pan, Yun
Gao, Yongliang
author_sort Chen, Aijun
collection PubMed
description 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/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.
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spelling pubmed-44270232015-05-14 The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes Chen, Aijun Huang, Xin Xue, Zhenan Cao, Di Huang, Kun Chen, Jin Pan, Yun Gao, Yongliang Med Sci Monit Basic Res Human Study 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/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. International Scientific Literature, Inc. 2015-04-30 /pmc/articles/PMC4427023/ /pubmed/25925725 http://dx.doi.org/10.12659/MSMBR.893608 Text en © Med Sci Monit, 2015 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License
spellingShingle Human Study
Chen, Aijun
Huang, Xin
Xue, Zhenan
Cao, Di
Huang, Kun
Chen, Jin
Pan, Yun
Gao, Yongliang
The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes
title The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes
title_full The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes
title_fullStr The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes
title_full_unstemmed The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes
title_short The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes
title_sort role of p21 in apoptosis, proliferation, cell cycle arrest, and antioxidant activity in uvb-irradiated human hacat keratinocytes
topic Human Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427023/
https://www.ncbi.nlm.nih.gov/pubmed/25925725
http://dx.doi.org/10.12659/MSMBR.893608
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