The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Functional consequences of caspase activation in cardiac myocytes
Open accessAbstract
Cardiomyocyte apoptosis is present in many cardiac disease states, including heart failure and ischemic heart disease. Apoptosis is associated with the activation of caspases that mediate the cleavage of vital and structural proteins. However, the functional contribution of apoptosis to these conditions is not known. Furthermore, in cardiac myocytes, apoptosis may not be complete, allowing the cells to persist for a prolonged period within the myocardium. Therefore, we examined whether caspase-3 cleaved cardiac myofibrillar proteins and, if so, whether it affects contractile function. The effects of caspase-3 were studied in vitro on individual components of the cardiac myofilament including α-actin, α-actinin, myosin heavy chain, myosin light chain 1/2, tropomyosin, cardiac troponins (T, I, C), and the trimeric troponin complex. Exposure of the myofibrillar protein (listed above) to caspase-3 for 4 h resulted in the cleavage of α-actin and α-actinin, but not myosin heavy chain, myosin light chain 1/2, and tropomyosin, into three fragments (30, 20, and 15 kDa) and one major fragment (45 kDa), respectively. When cTnT, cTnI, and cTnC were incubated individually with caspase-3, there was no detectable cleavage. However, when the recombinant troponin complex was exposed to caspase-3, cTnT was cleaved, resulting in fragments of 25 kDa. Furthermore, rat cardiac myofilaments exposed to caspase-3 exhibited similar patterns of myofibrillar protein cleavage. Treatment with the caspase inhibitor DEVD-CHO or z-VAD-fmk abolished the cleavage. Myofilaments, isolated from adult rat ventricular myocytes after induction of apoptotic pathway by using β-adrenergic stimulation, displayed a similar pattern of actin and TnT cleavage. Exposure of skinned fiber to caspase-3 decreased maximal Ca 2+ -activated force and myofibrillar ATPase activity. Our results indicate that caspase-3 cleaved myofibrillar proteins, resulting in an impaired force/Ca 2+ relationship and myofibrillar ATPase activity. Induction of apoptosis in cardiac cells was associated with similar cleavage of myofilaments. Therefore, activation of apoptotic pathways may lead to contractile dysfunction before cell death.
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“Besides the obvious role of apoptotic cell death in myocyte loss, activation of several proteases in the apoptotic cascade can cleave various contractile proteins (α-actin, α-actinin, α, β-myosin heavy chain, tropomyosin and troponins, Ref. 56), leading to deterioration in contractile function of the existing myocytes.”
From Cardiac remodeling in obesity (2008) · cites this paper as [56]
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Cites
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Apoptosis: controlled demolition at the cellular level
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Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
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A mechanistic role for cardiac myocyte apoptosis in heart failure
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Metadata
- Authors
- Communal, C., Sumandea, M., de Tombe, P., Narula, J., Solaro, R. J., & Hajjar, R. J.
- Affiliations
- Harvard University (US)
- Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129; Harvard Medical School, Boston, MA 02115; Department of Physiology and Biophysics, University of Illinois, Chicago, IL 60612; and Division of Cardiology, Medical College of Pennsylvania/Hanehmann, Philadelphia, PA 19102
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-04-23
- Volume
- 99
- Issue
- 9
- Pages
- 6252-6256
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC122935
- OpenAlex
- W2016568695
- Cited by
- 390
- References
- 23
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 10 · 2020: 10 · 2019: 7 · 2018: 18 · 2017: 9 · 2016: 15 · 2015: 13 · 2014: 17 · 2013: 18 · 2012: 17
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL‐62426)
- U.S. Public Health Service (R01-63704)
- National Heart, Lung, and Blood Institute (HL61557, HL-57623, F32HL010409, P01 HL 62426, F32HL10409-02, R01HL061557, P01HL062426)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- caspase-3, cardiomyocyte apoptosis, troponin T, troponin complex, cardiac contractile function, myofibrillar ATPase activity, calcium-activated force, beta-adrenergic stimulation, heart failure, ischemic heart disease, DEVD-CHO, z-VAD-fmk, ventricular myocytes
- MeSH terms
- Actinin, Actins, Adenosine Triphosphatases, Amino Acid Sequence, Animals, Cattle, Cells, Cultured, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Humans, Male, Molecular Sequence Data, Myocardium, Rabbits, Recombinant Proteins, Substrate Specificity, Time Factors, Tropomyosin, Troponin, Blotting, Western, Rats, Sprague-Dawley, Myosin Light Chains, Myosin Heavy Chains, Protein Isoforms, Caspases, Rats, Caspase 3
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