Troponin I Proteolysis and Myocardial Stunning: Now You See It—Now You Don»t

Canty, John M.; Lee, Techung

doi:10.1006/jmcc.2002.1531

Cited by 21 publications

(19 citation statements)

References 17 publications

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“…Examination of CTnI degradation showed that the C-terminal region of CTnI could be easily cleaved near amino acid 193 during myocardial stunning, producing a proteolytic fragment of a smaller molecular weight (∼26 kDa vs. 32 kDa of intact CTnI) (59). Studies in vitro showed that the cleavage occurs only in the presence of Ca 2+ and can be prevented by calpastatin, an inhibitor of the Ca 2+ -activated protease, calpain (60). In addition, it was shown that transgenic mice overexpressing this cleaved CTnI 1−193 protein developed left ventricular dysfunction and a contractile reserve to β-adrenergic stimulation (61).…”

Section: Troponin Imentioning

confidence: 99%

The Role of Troponins in Muscle Contraction

2002

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SummaryTroponin (Tn) is the sarcomeric Ca 2+ regulator for striated (skeletal and cardiac) muscle contraction. On binding Ca 2+ Tn transmits information via structural changes throughout the actintropomyosin filaments, activating myosin ATPase activity and muscle contraction. Although the Tn-mediated regulation of striated muscle contraction is now well understood, the role of different Tn isoforms in these processes is the subject of intensive investigations. This review addresses the physiological significance of the multiple Tn isoforms in skeletal and cardiac muscles as well as their role in the regulation of contraction.

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Section: Troponin Imentioning

confidence: 99%

The Role of Troponins in Muscle Contraction

2002

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“…Stunning without degradation and degradation without stunning were observed. 79 Prasan et al 80 investigated stunning in a rabbit model. They found no increase in troponin I fragmentation after reversible stunning, induced by 15 minutes of ischemia and 15 minutes of reperfusion, and they also showed that functional recovery was not related to troponin I breakdown.…”

Section: Degradation Of Thin Filament Proteinsmentioning

confidence: 99%

Modulation of Thin Filament Activation by Breakdown or Isoform Switching of Thin Filament Proteins

Marston

Redwood

2003

Circulation Research

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Abstract-In the heart, the contractile apparatus is adapted to the specific demands of the organ for continuous rhythmic contraction. The specialized contractile properties of heart muscle are attributable to the expression of cardiac-specific isoforms of contractile proteins. This review describes the isoforms of the thin filament proteins actin and tropomyosin and the three troponin subunits found in human heart muscle, how the isoform profiles of these proteins change during development and disease, and the possible functional consequences of these changes. During development of the heart, there is a distinctive switch of isoform expression at or shortly after birth; however, during adult life, thin filament protein isoform composition seems to be stable despite protein turnover rates of 3 to 10 days. The pattern of isoforms of actin, tropomyosin, troponin I, troponin C, and troponin T is not affected by aging or heart disease (ischemia and dilated cardiomyopathy). The evidence for proteolysis of thin filament proteins in situ during ischemia and stunning is evaluated, and it is concluded that C-terminal cleavage of troponin I is a feature of irreversibly injured myocardium but may not play a role in reversible stunning. Key Words: actin Ⅲ troponin Ⅲ tropomyosin Ⅲ calpain Ⅲ stunning T he contractile apparatus of muscle is made up from interdigitating thick and thin filaments arrayed in sarcomeres. Contraction is attributable to the sliding of thick filaments past thin filaments and is powered by the molecular motor of the myosin crossbridge cyclically attaching to actin, changing conformation, and detaching. Contractility is controlled by sarcoplasmic Ca 2ϩ , which acts on the receptor molecules troponin and tropomyosin in the thin filaments. 1 Native thin filaments are built up from a double helix of actin monomers, with the elongated tropomyosin molecule forming a continuous strand along each actin helix and the troponin complex bound every 7th actin. Troponin is made up from three subunits. Troponin I is the inhibitory protein that binds to actin and prevents myosin crossbridge cycling. Troponin C is the Ca 2ϩ -binding component; at micromolar Ca 2ϩ concentrations, Ca 2ϩ is bound to troponin C which then binds to troponin I, releasing it from its inhibitory site on actin. Troponin T is an elongated molecule that binds to both troponin C and troponin I and also to tropomyosin, thus anchoring the complex on the thin filament. The interaction Original received September 17, 2003; revision received October 20, 2003; accepted October 23, 2003. From the Imperial College London (S.B.M.), National Heart and Lung Institute, London, UK, and Department of Cardiovascular Medicine (C.S.R.), University of Oxford, UK.Correspondence to Steven B. Marston, Imperial College London, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, UK. E-mail S. Marston@imperial.ac.uk © 2003 American Heart Association, Inc. of the troponin complex with tropomyosin propagates the regulatory signal from 1 troponin to up to 14 a...

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“…4 In large-animal models, contractile dysfunction displayed by ischemically stunned canine and porcine myocardium has been attributed to intrinsic changes in myofilament sensitivity to calcium that may develop as a consequence of the dephosphorylation of phospholamban and troponin I after bouts of low-flow ischemia. 5,6 Because proteolysis of troponin I has not been observed consistently in larger animals, 2,[7][8][9] mechanisms that appear to mediate contractile dysfunction in rodents 10,11 may not modulate myocardial function in larger animals during and after low-flow ischemia. 4 Alterations in other cytoskeletal and myofibrillar proteins also are likely to influence contractile function.…”

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confidence: 99%

Myosin-Binding Protein C Phosphorylation, Myofibril Structure, and Contractile Function During Low-Flow Ischemia

Decker

Kulikovskaya

et al. 2005

Circulation

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Background-Contractile dysfunction develops in the chronically instrumented canine myocardium after bouts of low-flow ischemia and persists after reperfusion. The objective of this study is to identify whether changes in the phosphorylation state of myosin-binding protein C (MyBP-C) are a potential cause of dysfunction. Methods and Results-During low-flow ischemia, MyBP-C is dephosphorylated, and the number of actomyosin cross-bridges in the central core of the sarcomere decreases as thick filaments dissemble from the periphery of the myofibril. During reperfusion, MyBP-C remains dephosphorylated, and its degradation is accelerated. Conclusions-Dephosphorylation of MyBP-C may initiate changes in myofibril thick filament structure that decrease the interaction of myosin heads with actin thin filaments. Limiting the formation of actomyosin cross-bridges may contribute to the contractile dysfunction that is apparent after low-flow ischemia.

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Troponin I Proteolysis and Myocardial Stunning: Now You See It—Now You Don»t

Cited by 21 publications

References 17 publications

The Role of Troponins in Muscle Contraction

The Role of Troponins in Muscle Contraction

Modulation of Thin Filament Activation by Breakdown or Isoform Switching of Thin Filament Proteins

Myosin-Binding Protein C Phosphorylation, Myofibril Structure, and Contractile Function During Low-Flow Ischemia

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