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Cited by 40Cell death mechanisms and regulationSphingolipid Metabolism and SignalingCardiac Ischemia and Reperfusion

Involvement of caspase 3- and 8-like proteases in ceramide-induced apoptosis of cardiomyocytes

Wang, Jian, Zhen, Ling, Klug, Michael G., Wood, Dan, Wu, Xiying, Mizrahi, Jacques·2000·Journal of Cardiac Failure
DOI 10.1054/jcaf.2000.9502
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Abstract

Ceramides are the metabolic products of sphingolipids of the eukaryotic cell membranes and are believed to function as signaling molecules in a variety of biological processes. Ceramide induces apoptosis in cultured cardiomyocytes. However, the molecular pathway underlying ceramide-induced apoptosis is not clear. In this study, we investigated the role of the cysteinyl aspartate-specific proteases (caspases) in cardiomyocyte apoptosis induced by ceramide. Treatment of in vitro cultured rat neonatal cardiomyocytes with ceramide results in robust cell death, of which the majority is apoptotic, as shown by positive staining for terminal deoxyribonuclease transferase-mediated deoxyuridine triphosphate nick end-labeling and the appearance of pyknotic nuclei with Hoechst staining. Caspase 3- and 8-like protease activities are induced in cardiomyocytes by ceramide treatment. Addition of the tetrapeptide inhibitors for caspases attenuated ceramide-induced apoptosis. The nonselective caspase inhibitor (B-D-FMK) and the caspase 3 (Z-DEVD-FMK) and caspase 8 (Z-IETD-FMK) inhibitors reduced ceramide-induced cardiomyocyte death and significantly inhibited the activation of caspase 3. However, the inhibitors specific for caspases 1, 2, 4, 6, and 9 have no significant effects on cardiomyocyte survival under the same conditions. These data suggest that caspases 3- and 8-related proteases are involved in ceramide-induced cardiomyocyte apoptosis.

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Crossref · 10.1054/jcaf.2000.9502

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  • Increased concentrations of ceramide may mediate apoptosis in the heart in response to ischemia or drugs or cytokines that promote apoptosis.

    “Although there is much evidence that increased concentrations of ceramide may mediate apoptosis in the heart in response to ischemia or drugs or cytokines that promote apoptosis, will promote cytochrome c release and apoptosis when directly applied to cardiomyocytes, and that inhibition of de novo ceramide synthesis prevents palmitate-induced apoptosis in L6 myotubes (75, 82, 276, 355, 368), it”

    From Cardiac remodeling in obesity (2008) · cites this paper as [368]

  • Inhibition of de novo ceramide synthesis prevents palmitate-induced apoptosis in L6 myotubes.

    “Although there is much evidence that increased concentrations of ceramide may mediate apoptosis in the heart in response to ischemia or drugs or cytokines that promote apoptosis, will promote cytochrome c release and apoptosis when directly applied to cardiomyocytes, and that inhibition of de novo ceramide synthesis prevents palmitate-induced apoptosis in L6 myotubes (75, 82, 276, 355, 368), it”

    From Cardiac remodeling in obesity (2008) · cites this paper as [368]

  • Ceramide promotes cytochrome c release and apoptosis when directly applied to cardiomyocytes.

    “Although there is much evidence that increased concentrations of ceramide may mediate apoptosis in the heart in response to ischemia or drugs or cytokines that promote apoptosis, will promote cytochrome c release and apoptosis when directly applied to cardiomyocytes, and that inhibition of de novo ceramide synthesis prevents palmitate-induced apoptosis in L6 myotubes (75, 82, 276, 355, 368), it”

    From Cardiac remodeling in obesity (2008) · cites this paper as [368]

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Authors
Wang, J., Zhen, L., Klug, M. G., Wood, D., Wu, X., & Mizrahi, J.
Affiliations
Eli Lilly (United States) (US)
ORCID
Wu, Xiying
Venue
Journal of Cardiac Failure
Publisher
Elsevier BV
Published
2000-09
Volume
6
Issue
3
Pages
243-249
ISSN
1071-9164 (ISSN-L)
DOI
10.1054/jcaf.2000.9502
OpenAlex
W2160908368
Cited by
40
References
14
Citations by year
2026: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 2 · 2014: 1 · 2013: 1
FWCI
1.33
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Cardiac Failure (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
ceramide, apoptosis, cardiomyocytes, caspase-3, caspase-8, sphingolipids, caspase inhibitors, Z-DEVD-FMK, Z-IETD-FMK, neonatal cardiomyocytes, cell death signaling
MeSH terms
Animals, Ceramides, Heart, Myocardium, Oligopeptides, Cysteine Proteinase Inhibitors, Rats, Sprague-Dawley, Apoptosis, Cytoprotection, Caspases, Rats, Caspase 3, Caspase 8, Caspase 9, Caspase Inhibitors, In Vitro Techniques

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