© 1995 American Heart Association, Inc.
Articles |
Reperfusion of Rat Heart After Brief Ischemia Induces Proteolysis of Calspectin (Nonerythroid Spectrin or Fodrin) by Calpain
From the Departments of Legal Medicine (K.Y., K.H., Y.S.) and Pathology (T.I.), Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan; the Department of Neurochemistry and Neuropharmacology, Biomedical Research Center, Osaka University Medical School (M.I., K.S.), Suita, Osaka, Japan; and the Department of Molecular Biology, Tokyo (Japan) Metropolitan Institute of Medical Science (T.C.S., S.K.).
Correspondence to Ken-ichi Yoshida, MD, Department of Legal Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi 755, Japan.
Abstract Rat myocardium expresses the 240- and
235-kD polypeptides antigenically related to 
- and ß-subunits of
brain calspectin (nonerythroid spectrin or fodrin), respectively. In
the subcellular fractions of the myocardium, -calspectin
was found in the 600g, 10 000g, and
100 000g pellets, whereas ß-calspectin was localized to
the 10 000g pellet. On the basis of the
Na+,K+-ATPase activity and the contents
of a gap junction protein, the sarcolemma was distributed to the
10 000g and 100 000g pellets, and the
intercalated disks were enriched in the 10 000g pellet.
Both - and ß-calspectin were proteolyzed by calpain in vitro. The
two subunits were also proteolyzed in vivo, when the rat hearts
underwent 10 to 60 minutes of global ischemia followed by 30
minutes of reperfusion. The reperfusion following the ischemia
induced the proteolysis of -calspectin in the 10 000g
and 100 000g pellets, producing the 150-kD fragment. A
synthetic calpain inhibitor, calpain
inhibitor-1, suppressed the degradation of calspectin in
vivo, which indicates that calpain is responsible for the
reperfusion-induced proteolysis of calspectin. The
inhibitor also improved myocardial stunning.
Immunohistochemical study revealed that the proteolysis of
-calspectin occurs at the intercalated disks and the sarcolemma
after postischemic reperfusion, in accord with the
biochemical data. These results suggest that degradation of calspectin
partly accounts for the contractile failure of the
myocardium after postischemic reperfusion by
disrupting the membrane skeleton and the intercalated disks.
Key Words: ischemia • calspectin • fodrin • calpain • stunning
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