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http://purl.uniprot.org/citations/37949151http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37949151http://www.w3.org/2000/01/rdf-schema#comment"

Background

Ischemia and reperfusion (I/R) injury exacerbate the prognosis of ischemic diseases. The cause of this exacerbation is partly a mitochondrial cell death pathway. Mitochondrial calpain-5 is proteolyzed/autolyzed under endoplasmic reticulum stress, resulting in inflammatory caspase-4 activation. However, the role of calpain-5 in I/R injury remains unclear. We hypothesized that calpain-5 is involved in ischemic brain disease.

Methods

Mitochondria from C57BL/6J mice were extracted via centrifugation with/without proteinase K treatment. The expression and proteolysis/autolysis of calpain-5 were determined using western blotting. The mouse and human brains with I/R injury were analyzed using hematoxylin and eosin staining and immunohistochemistry. HT22 cells were treated with tunicamycin and CAPN5 siRNA.

Results

Calpain-5 was expressed in the mitochondria of mouse tissues. Mitochondrial calpain-5 in mouse brains was responsive to calcium earlier than cytosolic calpain-5 in vitro calcium assays and in vivo bilateral common carotid artery occlusion model mice. Immunohistochemistry revealed that neurons were positive for calpain-5 in the normal brains of mice and humans. The expression of calpain-5 was increased in reactive astrocytes at human infarction sites. The knockdown of calpain-5 suppressed of cleaved caspase-11.

Conclusions

The neurons of human and mouse brains express calpain-5, which is proteolyzed/autolyzed in the mitochondria in the early stage of I/R injury and upregulated in reactive astrocytes in the end-stage.

General significance

Our results provide a comprehensive understanding of the mechanisms underlying I/R injury. Targeting the expression or activity of mitochondrial calpain-5 may suppress the inflammation during I/R injuries such as cerebrovascular diseases."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.org/dc/terms/identifier"doi:10.1016/j.bbagen.2023.130506"xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/author"Itoh K."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/author"Fukuda T."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/author"Miki Y."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/author"Ozaki T."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/author"Wakabayashi K."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/author"Tomita H."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/author"Ito G."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/author"Sugano E."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/author"Chukai Y."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/date"2024"xsd:gYear
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/name"Biochim Biophys Acta Gen Subj"xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/pages"130506"xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/title"Role of calpain-5 in cerebral ischemia and reperfusion injury."xsd:string
http://purl.uniprot.org/citations/37949151http://purl.uniprot.org/core/volume"1868"xsd:string
http://purl.uniprot.org/citations/37949151http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/37949151
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