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Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes
Open accessAbstract
The energy need of cardiac muscle cells in vivo is largely covered by the oxidation of saturated and mono-unsaturated fatty acids (FA). However, in vitro studies have shown that the saturated FA C16:0 at physiological concentrations exerts detrimental effects on primary cultures of neonatal rat ventricular myocytes by, as yet, unknown mechanisms. To evaluate the noxious effects of FA in more detail, neonatal cardiomyocytes were exposed to saturated (C16:0; C18:0) or mono-unsaturated (C16:1; cis-C18:1; trans-C18:1) FA, or combinations thereof for up to 48 h. FA (0.5 mM) complexed to bovine serum albumin (BSA) (0.15 mM) were added to a glucose-containing defined medium. Irrespective of the length and degree of unsaturation of the aliphatic chain, FA supplied to the cells were readily incorporated in the phospholipid pool. In the presence of mono-unsaturated FA, cardiomyocytes remained healthy and accumulated substantial amounts of triacylglycerol. In contrast, within 24 h after application of the saturated FA C16:0 or C18:0, cells had become irreversibly damaged, as evidenced by the presence of pyknotic nuclei and massive release of the cytosolic markers lactate dehydrogenase (LDH) and fatty acid-binding protein (FABP). Moreover, the occurrence of DNA-laddering indicated that apoptosis was involved. Induction of apoptotic cell death by C16:0 was counteracted by the co-administration of equimolar amounts of cis-C18:1, whereas trans-C18:1 delayed, but did not prevent, loss of cardiomyocyte viability. The present findings suggest that the incorporation of saturated, but not mono-unsaturated, fatty acids induces alterations in the phospholipid membrane, which initiate apoptotic cell death in neonatal cardiomyocytes.
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“Studies examining the effects of altering dietary FA composition have suggested that diets with increased saturated fat content, or exposure of cultured cells to saturated FA promote apoptosis, which can be reversed by the addition of mono- or polyunsaturated FA (PUFA) (74, 212, 236, 260).”
From Cardiac remodeling in obesity (2008) · cites this paper as [74]
Citations
Cites
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S. A. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.493 · Cited by 9,444
Some statistical methods useful in circulation research.
Wallenstein, S., Zucker, C. L., & Fleiss, J. L. (1980) · Circulation Research · doi:10.1161/01.res.47.1.1 · Cited by 3,867
Apoptosis, oncosis, and necrosis. An overview of cell death.
Majno, G., & Joris, I. (1995) · PubMed · Cited by 3,328
Stubbs, C. D., & Smith, A. D. (1984) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(84)90005-4 · Cited by 1,618
Relationship Between Carbohydrate and Lipid Metabolism and the Energy Balance of Heart Muscle
Neely, J. R., & Morgan, H. E. (1974) · Annual Review of Physiology · doi:10.1146/annurev.ph.36.030174.002213 · Cited by 1,266
Krown, K. A., Pagé, M., Nguyen, C., Zechner, D., Gutierrez, V., Comstock, K. L., Glembotski, C. C., Quintana, P. J. E., & Sabbadini, R. A. (1996) · Journal of Clinical Investigation · doi:10.1172/jci119114 · Cited by 728
UV-Assay with Pyruvate and NADH
Bergmeyer, H. U., & Bernt, E. (1974) · Elsevier eBooks · doi:10.1016/b978-0-12-091302-2.50010-4 · Cited by 617
Fatty acid homeostasis in the normoxic and ischemic heart
Vusse, G. J., Glatz, J. F. C., Stam, H. C., & Reneman, R. S. (1992) · Physiological Reviews · doi:10.1152/physrev.1992.72.4.881 · Cited by 516
Chapter 1 Anatomical Methods in Cell Death
Kerr, J. F. R., Gobe, G. C., Winterford, C. M., & HARMON, B. V. (1995) · Methods in cell biology · doi:10.1016/s0091-679x(08)61921-4 · Cited by 469
Ionization and phase behavior of fatty acids in water: application of the Gibbs phase rule
Cistola, D. P., Hamilton, J. A., Jackson, D., & SMALL, D. M. (1988) · Biochemistry · doi:10.1021/bi00406a013 · Cited by 450
Iwaki, K., Sukhatme, V. P., Shubeita, H. E., & Chien, K. R. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)77420-6 · Cited by 443
Richieri, G. V., Anel, A., & Kleinfeld, A. M. (1993) · Biochemistry · doi:10.1021/bi00080a032 · Cited by 368
Paumen, M. B., Ishida, Y., Muramatsu, M., Yamamoto, M., & Honjo, T. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3324 · Cited by 349
Bishop, W. R., & Bell, R. M. (1988) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.04.110188.003051 · Cited by 270
Richieri, G. V., Ogata, R. T., & Kleinfeld, A. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35866-6 · Cited by 220
Cui, Z., Houweling, M., Chen, M. H., Record, M., Chap, H., Vance, D. E., & Tercé, F. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.14668 · Cited by 196
Kinsella, J. E., Bruckner, G. G., Mai, J., & Shimp, J. L. (1981) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/34.10.2307 · Cited by 185
Sheng, Z., Pennica, D., Wood, W. I., & Chien, K. R. (1996) · Development · doi:10.1242/dev.122.2.419 · Cited by 183
Lipid effects on the binding properties of a reconstituted insulin receptor.
Gould, R. J., Ginsberg, B. H., & Spector, A. A. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68389-4 · Cited by 126
Doi, O., Doi, F., Schroeder, F., Alberts, A. W., & Vagelos, P. R. (1978) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(78)90044-5 · Cited by 100
Relationship between Arachidonate−Phospholipid Remodeling and Apoptosis
Surette, M. E., Winkler, J. D., Fonteh, A. N., & Chilton, F. H. (1996) · Biochemistry · doi:10.1021/bi9530245 · Cited by 97
Galli, G., & Fratelli, M. (1993) · Experimental Cell Research · doi:10.1006/excr.1993.1008 · Cited by 97
The effects of long chain free fatty acids on human neutrophil function and structure.
Hawley, H. P., & Gordon, G. B. (1976) · PubMed · Cited by 85
Human tissue lipids: occurrence of fatty acid isomers from dietary hydrogenated oils.
Ohlrogge, J. B., Emken, E. A., & Gulley, R. M. (1981) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37333-8 · Cited by 84
Liscovitch, M. (1994) · Cell · doi:10.1016/0092-8674(94)90148-1 · Cited by 83
Dynamic modulation of mitochondrial membrane physical properties and ATPase activity by diet lipid
Innis, S. M., & Clandinin, M. T. (1981) · Biochemical Journal · doi:10.1042/bj1980167 · Cited by 64
Vork, M. M., Glatz, J. F. C., Surtel, D. A., Knubben, H. J. M., & Vusse, G. J. (1991) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(91)90267-k · Cited by 62
Self-citationButtke, T. M. (1984) · PubMed · Cited by 58
Phospholipase-A2-dependent signalling in the heart
van Bilsen, M., & Vusse, G. J. (1995) · Cardiovascular Research · doi:10.1016/s0008-6363(95)00098-4 · Cited by 52
Gradient of fatty acids from blood plasma to skeletal muscle in dogs
Vusse, G. J., & Roemen, T. H. M. (1995) · Journal of Applied Physiology · doi:10.1152/jappl.1995.78.5.1839 · Cited by 50
Self-citationRatnayake, W. M. N., Chen, Z., Pelletier, G., & Weber, D. F. (1994) · Lipids · doi:10.1007/bf02538915 · Cited by 46
Saturated free fatty acid toxicity
Gordon, G. B. (1977) · Experimental and Molecular Pathology · doi:10.1016/0014-4800(77)90035-1 · Cited by 44
Serum-myocardium gradients of non-esterified fatty acids in dog, rat and man
Vusse, G. J., Roemen, T. H. M., Flameng, W. J., & Reneman, R. S. (1983) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(83)90266-7 · Cited by 44
Self-citationVinculin, talin and focal adhesions
Goldmann, W. H., Ezzell, R. M., Adamson, E. D., Niggli, V., & Isenberg, G. (1996) · Journal of Muscle Research and Cell Motility · doi:10.1007/bf00140319 · Cited by 42
Singh, J. K., Dasgupta, A., Adayev, T., Shahmehdi, S. A., Hammond, D., & Banerjee, P. (1996) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/s0005-2760(96)00134-8 · Cited by 39
Long-chain fatty acid-binding to albumin: re-evaluation with directly measured concentrations
Rose, H., Conventz, M., Fischer, Y., Jüngling, E., Hennecke, T., & Kammermeier, H. (1994) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(94)90060-4 · Cited by 39
Arachidonic acid disrupts calcium dynamics in neonatal rat cardiac myocytes
Hoffmann, P., Richards, D. E., Heinroth‐Hoffmann, I., Mathias, P., Wey, H. E., & Toraason, M. A. (1995) · Cardiovascular Research · doi:10.1016/s0008-6363(95)00133-6 · Cited by 39
Rosenthal, M. D. (1981) · Lipids · doi:10.1007/bf02535435 · Cited by 38
INTERACTION OF FATTY ACID AND GLUCOSE OXIDATION BY CULTURED HEART CELLS
Rosenthal, M. D., & Warshaw, J. B. (1973) · The Journal of Cell Biology · doi:10.1083/jcb.58.2.332 · Cited by 30
The effects of saturated fatty acids on endothelial cells
Zhang, C., LYNGMO, V., & Nordøy, A. (1992) · Thrombosis Research · doi:10.1016/0049-3848(92)90226-z · Cited by 26
van der Loop, F. T. L., van Eys, G. J. J. M., Schaart, G., & Ramaekers, F. C. S. (1996) · Journal of Muscle Research and Cell Motility · doi:10.1007/bf00140321 · Cited by 24
Oxidation of oleic and elaidic acids in rat and human heart homogenates
Lanser, A. C., Emken, E. A., & Ohlrogge, J. B. (1986) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(86)90071-8 · Cited by 20
Peng, S., Crider, B. P., Tsai, S. J., Xie, X., & Stone, D. K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.6.3324 · Cited by 19
Hexeberg, S., Hessevik, I., & Hexeberg, E. (1995) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1995.tb09847.x · Cited by 17
Fatty acid and glucose oxidation by cultured rat heart cells
Rosenthal, M. D., & Warshaw, J. B. (1977) · Journal of Cellular Physiology · doi:10.1002/jcp.1040930106 · Cited by 16
Oxidation of carbohydrates and palmitate by intact cultured neonatal rat heart cells
Ross, P. D., & McCarl, R. L. (1984) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1984.246.3.h389 · Cited by 11
Anoxia in neonatal rat heart cell cultures
van der Laarse, A., ALTONA, J. C., & van Treslong, C. H. F. B. (1984) · Steinkopff eBooks · doi:10.1007/978-3-662-11041-6_27 · Cited by 6
Research works printed but not linked: 2
- De Vries, 1995, Saturated, but not mono-unsaturated, fatty acids induce cell death in neonatal rat ventricular cardiomyocytes. Eur, J. Physiol., S430:, R67
- Goligan, J. E., A. M. Kruisbeek, D. H. Margulies, E. M. Shevarh, and W. Strober, editors. 1991. Current Protocols for Immunology. Greene Publishing Associates and Wiley-Interscience, New York. 3.17.7-3.17.8.
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Schaffer, J. E. (2003) · Current Opinion in Lipidology · doi:10.1097/00041433-200306000-00008 · Cited by 933
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Metadata
- Authors
- de Vries, J. E., Vork, M. M., Roemen, T. H., de Jong, Y. F., Cleutjens, J. P., van der Vusse, G. J., & van Bilsen, M.
- Affiliations
- Maastricht University (NL)
- ORCID
- Cleutjens, J P
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 1997-07
- Volume
- 38
- Issue
- 7
- Pages
- 1384-1394
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2407618083
- Cited by
- 324
- References
- 47
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 3 · 2022: 7 · 2021: 12 · 2020: 8 · 2019: 8 · 2018: 9 · 2017: 9 · 2016: 14 · 2015: 9 · 2014: 7 · 2013: 21 · 2012: 16
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- saturated fatty acids, monounsaturated fatty acids, palmitic acid, stearic acid, cardiomyocyte apoptosis, neonatal rat ventricular myocytes, membrane damage, triglyceride accumulation, fatty acid oxidation, cardiotoxicity
- MeSH terms
- Fatty Acid-Binding Protein 7, Animals, Animals, Newborn, Carrier Proteins, Cells, Cultured, Culture Media, Fatty Acids, Fatty Acids, Monounsaturated, Glucose, Kinetics, L-Lactate Dehydrogenase, Myocardium, Neoplasm Proteins, Nerve Tissue Proteins, Phospholipids, Rats, Inbred WKY, Serum Albumin, Bovine, Triglycerides, Apoptosis, Myelin P2 Protein, Fatty Acid-Binding Proteins, Rats
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