Universität zu Köln

Naito, Masanori Gomi, Xu, Daichao, Amin, Palak ORCID: 0000-0001-5617-8703, Lee, Jinwoo, Wang, Huibing, Li, Wanjin, Kelliher, Michelle, Pasparakis, Manolis ORCID: 0000-0002-9870-0966 and Yuan, Junying ORCID: 0000-0003-2405-6036 (2020). Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke. Proc. Natl. Acad. Sci. U. S. A., 117 (9). S. 4959 - 4971. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Apoptosis and necroptosis are two regulated cell death mechanisms; however, the interaction between these cell death pathways in vivo is unclear. Here we used cerebral ischemia/reperfusion as a model to investigate the interaction between apoptosis and necroptosis. We show that the activation of RIPK1 sequentially promotes necroptosis followed by apoptosis in a temporally specific manner. Cerebral ischemia/reperfusion insult rapidly activates necroptosis to promote cerebral hemorrhage and neuroinflammation. Ripk3 deficiency reduces cerebral hemorrhage and delays the onset of neural damage mediated by inflammation. Reduced cerebral perfusion resulting from arterial occlusion promotes the degradation of TAK1, a suppressor of RIPK1, and the transition from necroptosis to apoptosis. Conditional knockout of TAK1 in microglial/infiltrated macrophages and neuronal lineages sensitizes to ischemic infarction by promoting apoptosis. Taken together, our results demonstrate the critical role of necroptosis in mediating neurovascular damage and hypoperfusion-induced TAK1 loss, which subsequently promotes apoptosis and cerebral pathology in stroke and neurodegeneration.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Naito, Masanori Gomi UNSPECIFIED UNSPECIFIED UNSPECIFIED Xu, Daichao UNSPECIFIED UNSPECIFIED UNSPECIFIED Amin, Palak UNSPECIFIED orcid.org/0000-0001-5617-8703 UNSPECIFIED Lee, Jinwoo UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Huibing UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Wanjin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kelliher, Michelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Yuan, Junying UNSPECIFIED orcid.org/0000-0003-2405-6036 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-341529
DOI:	10.1073/pnas.1916427117
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	117
Number:	9
Page Range:	S. 4959 - 4971
Date:	2020
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOCAL CEREBRAL-ISCHEMIA; PROGRAMMED NECROSIS; CELL-DEATH; KINASE; INJURY; INFLAMMATION; CONTRIBUTES; MECHANISMS; RECOVERY; NEURONS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/34152