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Role of calpain-5 in cerebral ischemia and reperfusion injury.
Chukai, Yusaku; Ito, Ginga; Miki, Yasuo; Wakabayashi, Koichi; Itoh, Ken; Sugano, Eriko; Tomita, Hiroshi; Fukuda, Tomokazu; Ozaki, Taku.
Afiliación
  • Chukai Y; Department of Biological Science, Graduate School of Science and Engineering, Iwate University, Iwate, Japan.
  • Ito G; Department of Biological Science, Graduate School of Science and Engineering, Iwate University, Iwate, Japan.
  • Miki Y; Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Aomori, Japan.
  • Wakabayashi K; Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Aomori, Japan.
  • Itoh K; Department of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, Aomori, Japan.
  • Sugano E; Department of Biological Science, Graduate School of Science and Engineering, Iwate University, Iwate, Japan.
  • Tomita H; Department of Biological Science, Graduate School of Science and Engineering, Iwate University, Iwate, Japan.
  • Fukuda T; Department of Biological Science, Graduate School of Science and Engineering, Iwate University, Iwate, Japan.
  • Ozaki T; Department of Biological Science, Graduate School of Science and Engineering, Iwate University, Iwate, Japan. Electronic address: tozaki@iwate-u.ac.jp.
Biochim Biophys Acta Gen Subj ; 1868(1): 130506, 2024 01.
Article en En | MEDLINE | ID: mdl-37949151
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Isquemia Encefálica Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Gen Subj Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Isquemia Encefálica Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Gen Subj Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos