UVB radiation induces apoptosis in keratinocytes by activating a pathway linked to "BLT2-reactive oxygen species"
- PMID:20090768
- DOI: 10.1038/jid.2009.436
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.
Similar articles
- Low-dose UVB irradiation stimulates matrix metalloproteinase-1 expression via a BLT2-linked pathway in HaCaT cells.Kim C, Ryu HC, Kim JH.Kim C, et al.Exp Mol Med. 2010 Dec 31;42(12):833-41. doi: 10.3858/emm.2010.42.12.086.Exp Mol Med. 2010.PMID:20966635Free PMC article.
- Role of the low-affinity leukotriene B4 receptor BLT2 in VEGF-induced angiogenesis.Kim GY, Lee JW, Cho SH, Seo JM, Kim JH.Kim GY, et al.Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):915-20. doi: 10.1161/ATVBAHA.109.185793. Epub 2009 Mar 12.Arterioscler Thromb Vasc Biol. 2009.PMID:19286633
- Pro-survival of estrogen receptor-negative breast cancer cells is regulated by a BLT2-reactive oxygen species-linked signaling pathway.Choi JA, Lee JW, Kim H, Kim EY, Seo JM, Ko J, Kim JH.Choi JA, et al.Carcinogenesis. 2010 Apr;31(4):543-51. doi: 10.1093/carcin/bgp203. Epub 2009 Sep 11.Carcinogenesis. 2010.PMID:19748928
- Identification, signaling, and functions of LTB4 receptors.Saeki K, Yokomizo T.Saeki K, et al.Semin Immunol. 2017 Oct;33:30-36. doi: 10.1016/j.smim.2017.07.010.Semin Immunol. 2017.PMID:29042026Review.
- Novel non-calcemic secosteroids that are produced by human epidermal keratinocytes protect against solar radiation.Slominski AT, Janjetovic Z, Kim TK, Wasilewski P, Rosas S, Hanna S, Sayre RM, Dowdy JC, Li W, Tuckey RC.Slominski AT, et al.J Steroid Biochem Mol Biol. 2015 Apr;148:52-63. doi: 10.1016/j.jsbmb.2015.01.014. Epub 2015 Jan 21.J Steroid Biochem Mol Biol. 2015.PMID:25617667Free PMC article.Review.
Cited by
- Photoprotective effects of Sargassum thunbergii on ultraviolet B-induced mouse L929 fibroblasts and zebrafish.Chen B, Chen H, Qu H, Qiao K, Xu M, Wu J, Su Y, Shi Y, Liu Z, Wang Q.Chen B, et al.BMC Complement Med Ther. 2022 May 21;22(1):144. doi: 10.1186/s12906-022-03609-x.BMC Complement Med Ther. 2022.PMID:35597942Free PMC article.
- Activation of the leukotriene B4 receptor 2-reactive oxygen species (BLT2-ROS) cascade following detachment confers anoikis resistance in prostate cancer cells.Lee JW, Kim JH.Lee JW, et al.J Biol Chem. 2013 Oct 18;288(42):30054-30063. doi: 10.1074/jbc.M113.481283. Epub 2013 Aug 28.J Biol Chem. 2013.PMID:23986446Free PMC article.
- Ras promotes transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition via a leukotriene B4 receptor-2-linked cascade in mammary epithelial cells.Kim H, Choi JA, Kim JH.Kim H, et al.J Biol Chem. 2014 Aug 8;289(32):22151-60. doi: 10.1074/jbc.M114.556126. Epub 2014 Jul 2.J Biol Chem. 2014.PMID:24990945Free PMC article.
- Quantum Sensing of Free Radical Generation in Mitochondria of Human Keratinocytes during UVB Exposure.Fan S, Lopez Llorens L, Perona Martinez FP, Schirhagl R.Fan S, et al.ACS Sens. 2024 May 24;9(5):2440-2446. doi: 10.1021/acssensors.4c00118. Epub 2024 May 14.ACS Sens. 2024.PMID:38743437Free PMC article.
- Suppression of the inflammatory response by oxyresveratrol from the root bark ofArtocarpus lakoocha Roxb against ultraviolet B-induced keratinocytes mediated by regulating p38 MAPK and AP-1.Malaniyom K, Ratanachamnong P, Namchaiw P, Namdaung U, Suksamrarn S, Jaisin Y.Malaniyom K, et al.Heliyon. 2024 Oct 11;10(20):e38962. doi: 10.1016/j.heliyon.2024.e38962. eCollection 2024 Oct 30.Heliyon. 2024.PMID:39469685Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources