Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes

Vries, J. E. De; Vork, M; Roemen, Theo H.M.; Jong, Y. F. De; Cleutjens, J. P. M.; Vusse, Ger J.; Bilsen, Marc van

doi:10.1016/s0022-2275(20)37421-6

Cited by 286 publications

(39 citation statements)

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“…Primary cultures of neonatal rat ventricular myocytes were prepared as described previously (8). Experiments were approved by the Institutional Animal Care and User Committee of the Maastricht University.…”

Section: Cell Culturementioning

confidence: 99%

“…The first experimental group received only glucose (final concentration 10 m m ) as substrate. The second group received a mixture of palmitic acid (C16:0) and oleic acid (C18:1) (0.25 m m each; complexed to 0.15 m m BSA as described elsewhere (8)). The third group received a combination of both substrates, i.e., glucose (10 m m ) and C16:0/C18:1 (0.25 m m each).…”

Section: Cell Culturementioning

confidence: 99%

“…After fixation of the cells in alcoholic formalin (90% ethanol, 4% formalin in doubly distilled H 2 O) at room temperature for 1 min, glycogen was visualized by periodic acid-Schiff (PAS) staining (11). Neutral lipids (triacylglycerols) were visualized with Oil Red-O (Aldrich Chemical Company, Milwaukee, WI) as described elsewhere (8). PAS-and Oil Red-O-stained cells were counterstained with hematoxylin (Sigma GHS-2-16).…”

Section: Cytochemistrymentioning

confidence: 99%

“…These observations prompted us to investigate in more detail the effects of long-chain fatty acids on cardiomyocyte phenotype in general and on the expression of genes encoding for proteins involved in glucose and fatty acid metabolism in particular. Primary cultures of neonatal rat ventricular cardiomyocytes were chosen as the model system, as the supply of substrates can be easily manipulated (8). In the present study the cardiomyocytes were incubated in minimal medium to which either glucose, fatty acids (palmitic acid and oleic acid complexed to albumin), or a combination of glucose and fatty acids had been added.…”

mentioning

confidence: 99%

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Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes

Lee

Vork

Vries

et al. 2000

Journal of Lipid Research

146

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Long-chain fatty acids are the most important substrates for the heart. In addition, they have been shown to affect signalling pathways and gene expression. To explore the effects of long-chain fatty acids on cardiac gene expression, neonatal rat ventricular myocytes were cultured for 48 h with either glucose (10 m M ), fatty acids (palmitic and oleic acid, 0.25 m M each), or a combination of both as exogenous substrates. Exposure to fatty acids (both in the absence or presence of glucose) neither affected cellular morphology and protein content nor induced alterations in the expression of phenotypic marker genes like atrial natriuretic factor and the Ca-ATPase SERCA2. However, incubation with fatty acids (with or without glucose) resulted in up to 4-fold increases of the mRNA levels of fatty acid translocase (FAT/CD36), heart-type fatty acid-binding protein, acyl-CoA synthetase, and long-chain acyl-CoA dehydrogenase. In contrast, the expression of genes coding for proteins involved in glucose uptake and metabolism, i.e., glucose transporter GLUT4, hexokinase II, and glyceraldehyde 3-phosphate dehydrogenase, remained constant or even declined under these conditions. These changes corresponded with a 60% increase in cardiomyocyte fatty acid oxidation capacity. Interestingly, the peroxisome proliferator-activated receptor-␣ (PPAR ␣ )-ligand Wy 14,643, but not the PPAR ␥ -ligand ciglitazone, also resulted in increased mRNA levels of genes involved in fatty acid metabolism.In conclusion, fatty acids specifically and co-ordinately up-regulate transcription of genes coding for proteins involved in cardiac fatty acid transport and metabolism, most likely through activation of PPAR ␣ . -van der Lee, K. A

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Section: Cell Culturementioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Section: Cytochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

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Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes

Lee

Vork

Vries

et al. 2000

Journal of Lipid Research

146

View full text Add to dashboard Cite

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“…In these two cases, the final concentration of FA in the medium was 160 and 40 times lower, respectively, than the concentrations used in the present study. In some other cases, neonatal cardiomyocytes have been cultured in the presence of FA-BSA complexes at concentrations similar to that used in the present study, but hypertrophy responses were not the primary focus of these particular studies (23)(24)(25). Nonetheless, chronic palmitate:oleate-BSA has been shown to induce many phenotypic changes in cardiomyocytes, including an increase in the rate of FA oxidation, an increase in the mRNA concentration of several genes involved in FA metabolism, and a decrease in the mRNA concentration of several genes involved in glucose metabolism (23).…”

Section: Discussionmentioning

confidence: 99%

Long-chain fatty acids modify hypertrophic responses of cultured primary neonatal cardiomyocytes

Zahabi

Deschepper

2001

Journal of Lipid Research

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In vivo, the normal heart obtains at least 60% of its energy from lipids and the remainder from glucose. Several lines of evidence indicate that an increase in the utilization of glucose [at the expense of fatty acids (FA)] may play a role in the genesis of hypertrophy. Primary cultures of neonatal cardiomyocytes have been used extensively to study the phenotype of these cells as well as their responses to hormonal hypertrophic agents. Unfortunately, such cultures are most typically cultured in glucose-rich FA-free media, and thus might be hypertrophied to start with. We therefore tested the effects of FAalbumin complexes on three different surrogate end points of hypertrophy of cardiomyocytes. Oleate-albumin complexes decreased the baseline values of all three variables, and increased the relative response of these variables to administration of norepinephrine. Oleate:palmitate-albumin complexes also affected all three variables and their responses to norepinephrine, but the effects differed somewhat from that of oleatealbumin complexes.Our results suggest that addition of long-chain FA, by providing conditions that more closely resemble physiological situations, may optimize the expression of hypertrophic responses in such cells. However, the differences between the effects of oleate and oleate:palmitate also suggest that the precise composition of FA may affect the phenotype of cardiomyocytes and how these cells respond to hypertrophic agents. -Zahabi, A., and C. F. Deschepper. Long-chain fatty acids modify hypertrophic responses of cultured primary neonatal cardiomyocytes.

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Molecular cloning of full-length cDNA encoding delta-9 desaturase through PCR strategies and its genomic organization and expression in grass carp (Ctenopharyngodon idella)

2001

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Desaturases are enzymes that catalyze double bond formation in fatty acids, which is a critical step in the synthesis of unsaturated fatty acids in organisms. Desaturase cDNA has been cloned from various species. Here we report the cloning of a full‐length cDNA of Δ9‐desaturase from grass carp (Ctenopharyngodon idella), using a combination of PCR techniques: reverse transcription–polymerase chain reaction (RT‐PCR) and rapid amplification of cDNA ends (RACE). The resolved cDNA encompasses 2420 bp, containing an open reading frame corresponding to 324 amino acids. The deduced amino acid sequence shares high homology with those of mammalian desaturases. Northern blot and RT‐PCR analyses demonstrated a high abundance of the transcript in liver tissue but low abundance in brain tissue. Furthermore, the structure of the gene has been resolved by screening its cognate genomic DNA library. The analysis shows that this gene is composed of six exons and five introns, encompassing a region of 8.5 kb. In particular, the last exon contains a length of the 3′ untranslated region as long as 1382 bp. Although the primary sequence and the genomic organization are phylogenetically conserved between fish and mammals, the regulation of the gene expression appears to be divergent among species. Mol. Reprod. Dev. 58:245–254, 2001. © 2001 Wiley‐Liss, Inc.

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Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes

Cited by 286 publications

References 40 publications

Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes

Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes

Long-chain fatty acids modify hypertrophic responses of cultured primary neonatal cardiomyocytes

Molecular cloning of full-length cDNA encoding delta-9 desaturase through PCR strategies and its genomic organization and expression in grass carp (Ctenopharyngodon idella)

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