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http://purl.uniprot.org/citations/16397188http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16397188http://www.w3.org/2000/01/rdf-schema#comment"

Background and purpose

Caspase-8 and caspase-9 are essential proteases of the extrinsic and intrinsic apoptotic pathways, respectively. We investigated whether neuroprotection associated with overexpression of heat-shock protein 70 (Hsp70), a natural cellular antiapoptotic protein, is mediated by caspase-8 and caspase-9 signaling in the neonatal mouse brain after hypoxia/ischemia (H/I) injury.

Methods

Postnatal day 7 transgenic mice overexpressing rat Hsp70 (Hsp70 Tg) and their wild-type (Wt) littermates underwent unilateral common carotid artery ligation followed by 30 minutes of exposure to 8% O2. The expression of apoptotic proteins was quantified by Western blot analysis, and the specific interaction between Hsp70 and apoptotic protease activating factor 1 (Apaf-1) was determined by coimmunoprecipitation.

Results

Hsp70 overexpression reduced cytosolic translocation of cytochrome c without affecting the levels of Apaf-1 and pro-caspase-9 24 hours after H/I. The expression of these apoptotic proteins in the naïve neonatal brains was also not affected by Hsp70 overexpression. Reduced caspase-9 cleavage occurred in Hsp70 Tg mice compared with Wt littermates 24 hours after H/I and correlated with increased binding of Hsp70 and Apaf-1. Increased cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP) expression and decreased caspase-8 cleavage were also observed in Hsp70 Tg compared with Wt mice 24 hours after H/I.

Conclusions

Our results suggest that the extrinsic and intrinsic apoptotic pathways mediate the neuroprotective effects of Hsp70 overexpression in neonatal H/I, specifically by upregulating FLIP and sequestering Apaf-1, leading to reduced cleavage of caspase-8 and caspase-9."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.org/dc/terms/identifier"doi:10.1161/01.str.0000199057.00365.20"xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/author"Hong S.M."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/author"Sheldon R.A."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/author"Kayama T."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/author"Matsumori Y."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/author"Ferriero D.M."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/author"Northington F.J."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/author"Weinstein P.R."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/author"Vexler Z.S."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/name"Stroke"xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/pages"507-512"xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/title"Reduction of caspase-8 and -9 cleavage is associated with increased c-FLIP and increased binding of Apaf-1 and Hsp70 after neonatal hypoxic/ischemic injury in mice overexpressing Hsp70."xsd:string
http://purl.uniprot.org/citations/16397188http://purl.uniprot.org/core/volume"37"xsd:string
http://purl.uniprot.org/citations/16397188http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16397188
http://purl.uniprot.org/citations/16397188http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/16397188
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http://purl.uniprot.org/uniprot/P0DMW0#attribution-68D7CF3D0595EB554876E58E404F2F5Ahttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/16397188
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http://purl.uniprot.org/uniprot/P0DMW1#attribution-68D7CF3D0595EB554876E58E404F2F5Ahttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/16397188
http://purl.uniprot.org/uniprot/#_A0A087WQT6-mappedCitation-16397188http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16397188
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