© 1999 American Heart Association, Inc.
Editorial |
Troponin I, Stunning, Hypertrophy, and Failure of the Heart
From the Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, Ill.
Correspondence to R. John Solaro, PhD, Department of Physiology and Biophysics (M/C 901), College of Medicine, University of Illinois at Chicago, 835 S Wolcott Ave, Chicago, IL 60612-7342.
Key Words: troponin I • hypertrophy • heart failure
Two articles1 2 in this issue of
Circulation Research point to the significance of the loss
of cardiac troponin I (cTnI) from the cell, the altered structure of
cTnI, and the altered function and interactions of cTnI as possible key
events in hypertrophy and ischemia/reperfusion
injury. These studies also provide strong evidence for the hypothesis
of Kusuoka and Marban,3 who first suggested that
stunning is associated with reversible breakdown and replacement of
damaged myofilament proteins. Later work from Marban's
laboratory4 identified cTnI proteolysis as the cause of
the reversible cardiac dysfunction in stunning. The results reported by
McDonough et al1 extend this and other
observations,5 6 correlating altered thin-filament
regulation with dysfunction resulting from cardiac stunning and more
severe episodes of ischemia with and without reperfusion. In
agreement with an earlier report5 suggesting that the
proteolysis of cTnI occurred between residues 188 and 199, McDonough et
al1 demonstrate that with moderate
ischemia/reperfusion, cTnI is degraded at its C-terminal end by
removal of 17 amino acids generating cTnI1–193.
With longer durations of ischemia and
ischemia/reperfusion, there is also an N-terminal truncation
generating 2 other degraded forms of the protein
(cTnI63–193 and
cTnI73–193). What is also new and potentially
important is evidence that cTnI1–193 forms a
covalent complex with the N-terminus of cTnC, a region that contains
the single regulatory Ca2+ binding domain, and
with the C-terminal residues of TnT that are important in transducing
the Ca2+ binding signal to tropomyosin (Tm).
McDonough et al1 propose that this complex formation
occurs through
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