Lovastatin does not accentuate but is rather additive to palmitate-induced apoptosis in cardiomyocytes.

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Kong JY, Rabkin SW

Lovastatin does not accentuate but is rather additive to palmitate-induced apoptosis in cardiomyocytes.

Prostaglandins Leukot Essent Fatty Acids. 2002 Nov;67(5):293-302.

PubMed ID

12445488 [ View in PubMed

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Abstract

Fatty acids such as palmitate have been observed to induce apoptosis in cardiomyocytes but the mechanism of this cytotoxicity is unresolved. The present study sought to determine whether an aspect of fatty acid metabolism is responsible for palmitate-induced apoptosis in cardiomyocytes. As palmitate metabolism increases acetyl CoA production via increased beta oxidation within the mitochondria, we hypothesized that increased acetyl CoA entering the cholesterol biosynthesis pathway might produce intermediates or end products that would be toxic to the cell. To test this hypothesis, cardiomyocytes from embryonic chick cardiomyocytes were treated with the 3-hydroxy-3-methylgutaryl CoA (HMG-CoA) reductase inhibitor lovastatin that inhibits the cholesterol biosynthesis pathway downstream of the acetyl CoA trimerization into HMG-CoA. Lovastatin did not inhibit palmitate-induced apoptosis. Rather, lovastatin induced significant apoptosis itself and when combined with palmitate, the level of apoptosis was equal to the sum of palmitate alone and lovastatin alone. This observation suggests that palmitate and lovastatin are inducing apoptosis by two independent mechanisms. A role for mitochondrial metabolism via carnitine palmitoyl transferase (CPT) in palmitate-induced apoptosis was suggested since capric acid, a fatty acid that is metabolized within the mitochondria but does not utilize CPT-1, did not induce apoptosis. Palmitate-induced apoptosis was further related to the metabolism of saturated fatty acids as the unsaturated fatty acid oleic acid did not induce apoptosis. These data suggest that a unique feature about palmitate metabolism independent of its role in cholesterol biosynthesis is responsible for palmitate-induced apoptosis and the effects of palmitate are additive to those of lovastatin to induce cardiac apoptosis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Levocarnitine	Carnitine O-palmitoyltransferase 2, mitochondrial	Protein	Humans	Unknown	Not Available	Details