Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1868, Issue 1, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbagen.2023.130506
Keywords
Mitochondria; Calpain-5; Neuronal cell death; Ischemia and reperfusion injury; Cerebrovascular disease; Endoplasmic reticulum stress
Categories
Ask authors/readers for more resources
The study found that mitochondrial calpain-5 plays an important role in the occurrence and development of ischemia-reperfusion injury and is expressed in the human and mouse brains. Targeting the expression or activity of mitochondrial calpain-5 may have significant implications for suppressing inflammation during I/R injuries such as cerebrovascular diseases.
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 calpain5 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available