Abstract | BACKGROUND/OBJECTIVES: METHODS AND RESULTS: Western blotting analysis showed the expression of μ- calpain, m-calpain and calpain 10 in mitochondria isolated from male Sprague-Dawley rats, but casein zymography detected only m-calpain activity. Subcellular fractionation of mitochondria demonstrated the distribution of m-calpain to the matrix fraction. Addition of >500μM of Ca(2+) to isolated mitochondria induced mitochondrial swelling, reflecting mPTP opening, and calpain activation. Ca(2+)-induced mitochondrial swelling was inhibited partially by the calpain inhibitor calpeptin. These results support a partial contribution of calpain in the opening of the mPTP. The addition of Ca(2+) to the mitochondria induced inactivation of complex I of the electron transport chain, and cleavage of the ND6 complex I subunit, which were inhibited by calpeptin. Mitochondria isolated from rat hearts that underwent 30min of coronary occlusion followed by 30min of reperfusion showed activation of mitochondrial calpains, ND6 cleavage, complex I inactivation, and mPTP opening, which were inhibited by pretreatment with calpain inhibitor 1. CONCLUSIONS: We demonstrated for the first time the presence of mitochondrial matrix m- calpain, and its contribution to complex I inactivation and mPTP opening after postischemic reperfusion in the rat heart.
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Authors | Kaori Shintani-Ishida, Ken-Ichi Yoshida |
Journal | International journal of cardiology
(Int J Cardiol)
Vol. 197
Pg. 26-32
(Oct 15 2015)
ISSN: 1874-1754 [Electronic] Netherlands |
PMID | 26113472
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Dipeptides
- Mitochondrial Membrane Transport Proteins
- Mitochondrial Permeability Transition Pore
- calpeptin
- Calpain
- m-calpain
- Calcium
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Topics |
- Animals
- Blotting, Western
- Calcium
(pharmacology)
- Calpain
(antagonists & inhibitors, pharmacology)
- Dipeptides
(pharmacology)
- Female
- Humans
- Male
- Middle Aged
- Mitochondria, Heart
(enzymology)
- Mitochondrial Membrane Transport Proteins
(metabolism)
- Mitochondrial Permeability Transition Pore
- Myocardial Reperfusion Injury
(enzymology)
- Rats
- Rats, Sprague-Dawley
- Young Adult
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