RIP1 and RIP3 mediate hemin-induced cell death in HT22 hippocampal neuronal cells

Xingfen Su,1 Handong Wang,2 Yuanxiang Lin,1 Fuxiang Chen1 1Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, People’s Republic of China; 2Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanj...

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Autores principales:	Su X, Wang H, Lin Y, Chen F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	intracerebral hemorrhage necroptosis TH22 RIP1 RIP3 necrostatin-1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/5adb13fa477545dd9db2c30408678aa2
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spelling	oai:doaj.org-article:5adb13fa477545dd9db2c30408678aa22021-12-02T01:59:31ZRIP1 and RIP3 mediate hemin-induced cell death in HT22 hippocampal neuronal cells1178-2021https://doaj.org/article/5adb13fa477545dd9db2c30408678aa22018-11-01T00:00:00Zhttps://www.dovepress.com/rip1-and-rip3-mediate-hemin-induced-cell-death-in-ht22-hippocampal-neu-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Xingfen Su,1 Handong Wang,2 Yuanxiang Lin,1 Fuxiang Chen1 1Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, People’s Republic of China; 2Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu, People’s Republic of China Background: Intracerebral hemorrhage (ICH) is a devastating neurological injury associated with significant mortality. Necroptosis is a newly identified type of programmed necrosis initiated by the activation of tumor necrosis factor alpha. Evidences had demonstrated the importance of necroptosis in neuronal cell death. Necrostatin-1 is a specific inhibitor of necroptosis. The present study was carried out to explore whether RIP1/RIP3 pathways participate in hemin induced cell death in HT-22 hippocampal neuronal cells and investigate the potential neuroprotection of necrostatin-1 in hemin induced cell death in HT-22. Methods: First, different concentrations of hemin (0, 25, 50, 100 µmol/L) were added to HT-22 cells. Propidium iodide (PI) positive cells and cell viability were measured at 24 hours after hemin treatment. Then, necrostatin-1, pan-caspase inhibitor Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk) and reactive oxygen species (ROS) scavenger butylated hydroxyanisole (BHA) were applied to hemin-treated HT-22 cells. PI positive cells and cell viability were measured at 24 hours after hemin treatment. MitoSox Red was used to indicate ROS level. Last, the effect of RIP3 in hemin induced HT-22 cell death was explored through RIP3 knockdown using siRNA. PI positive cells, cell viability and ROS lever were measured at 24 h after hemin treatment. Results: Hemin could induce a dose dependent cell death in HT22 neural cells. RIP1 specific inhibitor necrostatin-1 significantly inhibited cell death induced by hemin in HT-22 cells, greatly reducing PI positive cells, dramatically improving cell viability and decreasing ROS accumulation. BHA could significantly inhibit PI positive cells induced by hemin in HT-22 cells. Furthermore, silencing of RIP3 using siRNA attenuated hemin induced cell death in HT-22 cells, greatly reducing PI positive cells, dramatically improving cell viability and decreasing ROS accumulation. Conclusion: These data revealed that RIP1/RIP3 might mediate hemin induced cell death in HT-22 cells, and necrostatin-1 played a neuroprotection role in hemin induced cell death in HT-22. RIP1 and RIP3 might represent novel therapeutic targets for ICH. Keywords: intracerebral hemorrhage, necroptosis, HT22, RIP1, RIP3, necrostatin-1Su XWang HLin YChen FDove Medical Pressarticleintracerebral hemorrhagenecroptosisTH22RIP1RIP3necrostatin-1Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 14, Pp 3111-3119 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	intracerebral hemorrhage necroptosis TH22 RIP1 RIP3 necrostatin-1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	intracerebral hemorrhage necroptosis TH22 RIP1 RIP3 necrostatin-1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Su X Wang H Lin Y Chen F RIP1 and RIP3 mediate hemin-induced cell death in HT22 hippocampal neuronal cells
description	Xingfen Su,1 Handong Wang,2 Yuanxiang Lin,1 Fuxiang Chen1 1Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, People’s Republic of China; 2Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu, People’s Republic of China Background: Intracerebral hemorrhage (ICH) is a devastating neurological injury associated with significant mortality. Necroptosis is a newly identified type of programmed necrosis initiated by the activation of tumor necrosis factor alpha. Evidences had demonstrated the importance of necroptosis in neuronal cell death. Necrostatin-1 is a specific inhibitor of necroptosis. The present study was carried out to explore whether RIP1/RIP3 pathways participate in hemin induced cell death in HT-22 hippocampal neuronal cells and investigate the potential neuroprotection of necrostatin-1 in hemin induced cell death in HT-22. Methods: First, different concentrations of hemin (0, 25, 50, 100 µmol/L) were added to HT-22 cells. Propidium iodide (PI) positive cells and cell viability were measured at 24 hours after hemin treatment. Then, necrostatin-1, pan-caspase inhibitor Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk) and reactive oxygen species (ROS) scavenger butylated hydroxyanisole (BHA) were applied to hemin-treated HT-22 cells. PI positive cells and cell viability were measured at 24 hours after hemin treatment. MitoSox Red was used to indicate ROS level. Last, the effect of RIP3 in hemin induced HT-22 cell death was explored through RIP3 knockdown using siRNA. PI positive cells, cell viability and ROS lever were measured at 24 h after hemin treatment. Results: Hemin could induce a dose dependent cell death in HT22 neural cells. RIP1 specific inhibitor necrostatin-1 significantly inhibited cell death induced by hemin in HT-22 cells, greatly reducing PI positive cells, dramatically improving cell viability and decreasing ROS accumulation. BHA could significantly inhibit PI positive cells induced by hemin in HT-22 cells. Furthermore, silencing of RIP3 using siRNA attenuated hemin induced cell death in HT-22 cells, greatly reducing PI positive cells, dramatically improving cell viability and decreasing ROS accumulation. Conclusion: These data revealed that RIP1/RIP3 might mediate hemin induced cell death in HT-22 cells, and necrostatin-1 played a neuroprotection role in hemin induced cell death in HT-22. RIP1 and RIP3 might represent novel therapeutic targets for ICH. Keywords: intracerebral hemorrhage, necroptosis, HT22, RIP1, RIP3, necrostatin-1
format	article
author	Su X Wang H Lin Y Chen F
author_facet	Su X Wang H Lin Y Chen F
author_sort	Su X
title	RIP1 and RIP3 mediate hemin-induced cell death in HT22 hippocampal neuronal cells
title_short	RIP1 and RIP3 mediate hemin-induced cell death in HT22 hippocampal neuronal cells
title_full	RIP1 and RIP3 mediate hemin-induced cell death in HT22 hippocampal neuronal cells
title_fullStr	RIP1 and RIP3 mediate hemin-induced cell death in HT22 hippocampal neuronal cells
title_full_unstemmed	RIP1 and RIP3 mediate hemin-induced cell death in HT22 hippocampal neuronal cells
title_sort	rip1 and rip3 mediate hemin-induced cell death in ht22 hippocampal neuronal cells
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/5adb13fa477545dd9db2c30408678aa2
work_keys_str_mv	AT sux rip1andrip3mediatehemininducedcelldeathinht22hippocampalneuronalcells AT wangh rip1andrip3mediatehemininducedcelldeathinht22hippocampalneuronalcells AT liny rip1andrip3mediatehemininducedcelldeathinht22hippocampalneuronalcells AT chenf rip1andrip3mediatehemininducedcelldeathinht22hippocampalneuronalcells
_version_	1718402777736019968

RIP1 and RIP3 mediate hemin-induced cell death in HT22 hippocampal neuronal cells

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