UVB radiation induces apoptosis in keratinocytes by activating a pathway linked to BLT2-reactive oxygen species

Ho Cheol Ryu; Cheolmin Kim; Joo Young Kim; Jin Ho Chung; Jae Hong Kim

doi:10.1038/jid.2009.436

UVB radiation induces apoptosis in keratinocytes by activating a pathway linked to BLT2-reactive oxygen species

Ho Cheol Ryu, Cheolmin Kim, Joo Young Kim, Jin Ho Chung, Jae Hong Kim

Division of life Sciences

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50 Citations (Scopus)

Abstract

The role of reactive oxygen species (ROS) in UVB-induced apoptosis has been established, but the molecular mechanisms of their production in response to UVB irradiation in keratinocytes are not well understood. In this study, we demonstrate that levels of BLT2, a low-affinity leukotriene B 4 receptor, and its ligands (LTB 4 and 12(S)-HETE) are greatly increased by UVB irradiation and are responsible for the UVB-induced ROS generation in human keratinocytes. Blockade of BLT2 with a BLT2-specific antagonist, LY255283, or with siBLT2 attenuated ROS production and apoptotic cell death detected by a number of criteria. Moreover, we found that the NADPH oxidase family protein Nox1 lies downstream of BLT2 and mediates UVB-induced ROS production and apoptosis. Topical treatment of mouse epidermal skin with LY255283 gave significant protection against UVB-induced sunburn-associated apoptotic damage. Finally, when BLT2-overexpressing transgenic mice were irradiated with UVB, we observed more extensive skin apoptosis. Taken together, our results demonstrate that a BLT2-Nox1-linked pathway has a crucial role in UVB-induced ROS generation and mediates apoptosis in human keratinocytes.

Original language	English
Pages (from-to)	1095-1106
Number of pages	12
Journal	Journal of Investigative Dermatology
Volume	130
Issue number	4
DOIs	https://doi.org/10.1038/jid.2009.436
Publication status	Published - 2010 Apr

Bibliographical note

Funding Information:
We sincerely thank Dr T Shimizu (University of Tokyo, Tokyo, Japan) and Dr T Yokomizo (University of Kyushu, Fukuoka, Japan) for the BLT2 expression plasmids, and Dr YS Bae (Ewha Women's University, Seoul, Korea) for the human siNox1 construct. This work was supported by the SRC program (Aging and Apoptosis Research), the Diseases Network Research Program from the Ministry of Education, Science & Technology, Korea, and a Korea Research Foundation grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2008-3130C00603).

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Dermatology
Cell Biology

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10.1038/jid.2009.436

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title = "UVB radiation induces apoptosis in keratinocytes by activating a pathway linked to BLT2-reactive oxygen species",

abstract = "The role of reactive oxygen species (ROS) in UVB-induced apoptosis has been established, but the molecular mechanisms of their production in response to UVB irradiation in keratinocytes are not well understood. In this study, we demonstrate that levels of BLT2, a low-affinity leukotriene B 4 receptor, and its ligands (LTB 4 and 12(S)-HETE) are greatly increased by UVB irradiation and are responsible for the UVB-induced ROS generation in human keratinocytes. Blockade of BLT2 with a BLT2-specific antagonist, LY255283, or with siBLT2 attenuated ROS production and apoptotic cell death detected by a number of criteria. Moreover, we found that the NADPH oxidase family protein Nox1 lies downstream of BLT2 and mediates UVB-induced ROS production and apoptosis. Topical treatment of mouse epidermal skin with LY255283 gave significant protection against UVB-induced sunburn-associated apoptotic damage. Finally, when BLT2-overexpressing transgenic mice were irradiated with UVB, we observed more extensive skin apoptosis. Taken together, our results demonstrate that a BLT2-Nox1-linked pathway has a crucial role in UVB-induced ROS generation and mediates apoptosis in human keratinocytes.",

author = "Ryu, {Ho Cheol} and Cheolmin Kim and Kim, {Joo Young} and Chung, {Jin Ho} and Kim, {Jae Hong}",

note = "Funding Information: We sincerely thank Dr T Shimizu (University of Tokyo, Tokyo, Japan) and Dr T Yokomizo (University of Kyushu, Fukuoka, Japan) for the BLT2 expression plasmids, and Dr YS Bae (Ewha Women's University, Seoul, Korea) for the human siNox1 construct. This work was supported by the SRC program (Aging and Apoptosis Research), the Diseases Network Research Program from the Ministry of Education, Science & Technology, Korea, and a Korea Research Foundation grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2008-3130C00603). ",

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AU - Kim, Jae Hong

N1 - Funding Information: We sincerely thank Dr T Shimizu (University of Tokyo, Tokyo, Japan) and Dr T Yokomizo (University of Kyushu, Fukuoka, Japan) for the BLT2 expression plasmids, and Dr YS Bae (Ewha Women's University, Seoul, Korea) for the human siNox1 construct. This work was supported by the SRC program (Aging and Apoptosis Research), the Diseases Network Research Program from the Ministry of Education, Science & Technology, Korea, and a Korea Research Foundation grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2008-3130C00603).

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N2 - The role of reactive oxygen species (ROS) in UVB-induced apoptosis has been established, but the molecular mechanisms of their production in response to UVB irradiation in keratinocytes are not well understood. In this study, we demonstrate that levels of BLT2, a low-affinity leukotriene B 4 receptor, and its ligands (LTB 4 and 12(S)-HETE) are greatly increased by UVB irradiation and are responsible for the UVB-induced ROS generation in human keratinocytes. Blockade of BLT2 with a BLT2-specific antagonist, LY255283, or with siBLT2 attenuated ROS production and apoptotic cell death detected by a number of criteria. Moreover, we found that the NADPH oxidase family protein Nox1 lies downstream of BLT2 and mediates UVB-induced ROS production and apoptosis. Topical treatment of mouse epidermal skin with LY255283 gave significant protection against UVB-induced sunburn-associated apoptotic damage. Finally, when BLT2-overexpressing transgenic mice were irradiated with UVB, we observed more extensive skin apoptosis. Taken together, our results demonstrate that a BLT2-Nox1-linked pathway has a crucial role in UVB-induced ROS generation and mediates apoptosis in human keratinocytes.

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UVB radiation induces apoptosis in keratinocytes by activating a pathway linked to BLT2-reactive oxygen species

Abstract

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