Role of regulatory proteins (troponin-tropomyosin) in pathologic states.
In vertebrate striated muscle, troponin-tropomyosin is responsible, in part, not only for transducing the effect of calcium on contractile protein activation, but also for inhibiting actin and myosin interaction when calcium is absent. The regulatory troponin (Tn) complex displays several molecular and calcium binding variations in cardiac muscles of different species and undergoes genetic changes with development and in various pathologic states. Extensive reviews on the role of tropomyosin (Tm) and Tn in the regulation of striated muscle contraction have been published describing the molecular mechanisms involved in contractile protein regulation. In our studies, we have found an increase in Mg2+ ATPase activity in cardiac myofibrils from dystrophic hamsters and in rats with chronic coronary artery narrowing. The abnormalities in myofibrillar ATPase activity from cardiomyopathic hamsters were largely corrected by recombining the preparations with a TnTm complex isolated from normal hamsters indicating that the TnTm may play a major role in altered myocardial function. We have also observed down regulation of Ca2+ Mg2+ ATPase of myofibrils from hypertrophic guinea pig hearts, myocardial infarcted rats and diabetic-hypertensive rat hearts. In myosin from diabetic rats, this abnormality was substantially corrected by adding troponin-tropomyosin complex from control hearts. All of these disease models are associated with decreased ATPase activities of pure myosin and in the case of rat and hamster models, shifts of myosin heavy chain from alpha to beta predominate. In summary, there are three main troponin subunit components which might alter myofibrillar function however, very few direct links of molecular alterations in the regulatory proteins to physiologic and pathologic function have been demonstrated so far.
Malhotra
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Department of Medicine, Montefiore Medical Center, Bronx, NY 10467.
D000199:Actins / Q000737:chemistry / Q000502:physiology; D000818:Animals; D001419:Bacteria / Q000378:metabolism; D006801:Humans; D013329:Structure-Activity Relationship; D014335:Tropomyosin / Q000737:chemistry / Q000502:physiology*; D014336:Troponin / Q000737:chemistry / Q000502:physiology*
D000199:Actins; D014335:Tropomyosin; D014336:Troponin; C042260:troponin-tropomyosin complex