Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death

Abstract Ultraviolet (UV) is one of the most energetic radiations in the solar spectrum that can result in various tissue injury disorders. Previous studies demonstrated that UVA, which represents 95% of incident photovoltaic radiation, induces corneal endothelial cells (CECs) death. Programmed cell...

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Autores principales:	Zhen Yu, Nikolaos E. Efstathiou, Victor S. M. C. Correa, Xiaohong Chen, Kenji Ishihara, Yasuhiro Iesato, Toshio Narimatsu, Dimitrios Ntentakis, Yanyun Chen, Demetrios G. Vavvas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/8671ea8f9ed74a8d8ee6d62a9c472bc4
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spelling	oai:doaj.org-article:8671ea8f9ed74a8d8ee6d62a9c472bc42021-11-28T12:10:38ZReceptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death10.1038/s41420-021-00757-w2058-7716https://doaj.org/article/8671ea8f9ed74a8d8ee6d62a9c472bc42021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00757-whttps://doaj.org/toc/2058-7716Abstract Ultraviolet (UV) is one of the most energetic radiations in the solar spectrum that can result in various tissue injury disorders. Previous studies demonstrated that UVA, which represents 95% of incident photovoltaic radiation, induces corneal endothelial cells (CECs) death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor-interacting protein 3 kinase (RIPK3), a key signaling molecule of PCD, in UVA-induced injury using a short-term corneal endothelium (CE) culture model. UVA irradiation activated RIPK3 and mediated necroptosis both in mouse CE and primary human CECs (pHCECs). UVA irradiation was associated with upregulation of key necroptotic molecules (DAI, TRIF, and MLKL) that lie downstream of RIPK3. Moreover, RIPK3 inhibition or silencing in primary corneal endothelial cells suppresses UVA-induced cell death, along with downregulation of MLKL in pHCECs. In addition, genetic inhibition or knockout of RIPK3 in mice (RIPK3K51A and RIPK3−/− mice) similarly attenuates cell death and the levels of necroptosis in ex vivo UVA irradiation experiments. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced cell death in CE and indicate its potential as a future protective target.Zhen YuNikolaos E. EfstathiouVictor S. M. C. CorreaXiaohong ChenKenji IshiharaYasuhiro IesatoToshio NarimatsuDimitrios NtentakisYanyun ChenDemetrios G. VavvasNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Zhen Yu Nikolaos E. Efstathiou Victor S. M. C. Correa Xiaohong Chen Kenji Ishihara Yasuhiro Iesato Toshio Narimatsu Dimitrios Ntentakis Yanyun Chen Demetrios G. Vavvas Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death
description	Abstract Ultraviolet (UV) is one of the most energetic radiations in the solar spectrum that can result in various tissue injury disorders. Previous studies demonstrated that UVA, which represents 95% of incident photovoltaic radiation, induces corneal endothelial cells (CECs) death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor-interacting protein 3 kinase (RIPK3), a key signaling molecule of PCD, in UVA-induced injury using a short-term corneal endothelium (CE) culture model. UVA irradiation activated RIPK3 and mediated necroptosis both in mouse CE and primary human CECs (pHCECs). UVA irradiation was associated with upregulation of key necroptotic molecules (DAI, TRIF, and MLKL) that lie downstream of RIPK3. Moreover, RIPK3 inhibition or silencing in primary corneal endothelial cells suppresses UVA-induced cell death, along with downregulation of MLKL in pHCECs. In addition, genetic inhibition or knockout of RIPK3 in mice (RIPK3K51A and RIPK3−/− mice) similarly attenuates cell death and the levels of necroptosis in ex vivo UVA irradiation experiments. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced cell death in CE and indicate its potential as a future protective target.
format	article
author	Zhen Yu Nikolaos E. Efstathiou Victor S. M. C. Correa Xiaohong Chen Kenji Ishihara Yasuhiro Iesato Toshio Narimatsu Dimitrios Ntentakis Yanyun Chen Demetrios G. Vavvas
author_facet	Zhen Yu Nikolaos E. Efstathiou Victor S. M. C. Correa Xiaohong Chen Kenji Ishihara Yasuhiro Iesato Toshio Narimatsu Dimitrios Ntentakis Yanyun Chen Demetrios G. Vavvas
author_sort	Zhen Yu
title	Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death
title_short	Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death
title_full	Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death
title_fullStr	Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death
title_full_unstemmed	Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death
title_sort	receptor interacting protein 3 kinase, not 1 kinase, through mlkl-mediated necroptosis is involved in uva-induced corneal endothelium cell death
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/8671ea8f9ed74a8d8ee6d62a9c472bc4
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Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death

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