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Fatty acids resources:

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Life Sci. 2002 May 31;71(2):153-61.
Increased oxidative stress and decreased activities of Ca(2+)/Mg(2+)-ATPase and Na(+)/K(+)-ATPase in the red blood cells of the hibernating black bear.

Chauhan VP, Tsiouris JA, Chauhan A, Sheikh AM, Brown WT, Vaughan M.

NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. chauhanvpol.com

During hibernation, animals undergo metabolic changes that result in reduced utilization of glucose and oxygen. Fat is known to be the preferential source of energy for hibernating animals. Malonyldialdehyde (MDA) is an end product of fatty acid oxidation, and is generally used as an index of lipid peroxidation. We report here that peroxidation of lipids is increased in the plasma and in the membranes of red blood cells in black bears during hibernation. The plasma MDA content was about four fold higher during hibernation as compared to that during the active, non-hibernating state (P < 0.0001). Similarly, MDA content of erythrocyte membranes was significantly increased during hibernation (P < 0.025). The activity of Ca(2+)/Mg(2+)-ATPase in the erythrocyte membrane was significantly decreased in the hibernating state as compared to the active state. Na(+)/K(+)-ATPase activity was also decreased, though not significant, during hibernation. These results suggest that during hibernation, the bears are under increased oxidative stress, and have reduced activities of membrane-bound enzymes such as Ca(2+)/Mg(2+)-ATPase and Na(+)/K(+)-ATPase. These changes can be considered part of the adaptive for survival process of metabolic depression.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12031685&dopt=Abstract

Cardiovasc Res. 2002 Jun;54(3):601-10.
Differential effects of docosahexaenoic acid on contractions and L-type Ca2+ current in adult cardiac myocytes.

Ferrier GR, Redondo I, Zhu J, Murphy MG.

Department of Pharmacology, Sir Charles Tupper Medical Bldg., Dalhousie University, Nova Scotia, Halifax, Canada. gregory.ferrieal.ca

Beneficial effects of n-3 polyunsaturated fatty acids in Ca2+ overload have been attributed to blockade of L-type Ca2+ current (I(Ca-L)). However, cardiac contractions may be maintained despite block of I(Ca-L). OBJECTIVE: This study investigates the cellular basis by which docosahexaenoic acid (DHA), a representative n-3 polyunsaturated fatty acid, inhibits I(Ca-L) while preserving contraction. METHODS: Experiments were conducted in adult guinea pig ventricular myocytes with Na+ currents blocked. Contractions initiated by the voltage-sensitive release mechanism (VSRM) and calcium-induced calcium release (CICR) triggered by I(Ca-L), were activated separately with voltage clamp techniques. RESULTS: DHA (10 microM) inhibited I(Ca-L) and CICR contractions but not VSRM contractions. CICR contractions exhibited a bell-shaped voltage-dependence. However, in the presence of DHA, only contractions with a sigmoidal voltage-dependence characteristic of the VSRM remained. These contractions exhibited inactivation properties characteristic of the VSRM. DHA abolished I(Ca-L) elicited by test steps from -40 mV. Block was voltage-dependent, as residual I(Ca-L) was elicited by steps from -70 mV. Cd2+ inhibited residual current, but not contractions initiated by the same activation steps. CONCLUSION: Preservation of VSRM contractions during block of I(Ca-L), may explain the ability of n-3 polyunsaturated fatty acids to inhibit Ca2+ influx while preserving cardiac contractile function.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12031706&dopt=Abstract

Free Radic Biol Med. 2002 Jun 1;32(11):1123-31.
The effects of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids on the transcription of genes regulating their uptake and metabolism by the liver: influence of cellular oxidative state.

Zheng X, Rivabene R, Cavallari C, Napolitano M, Avella M, Bravo E, Botham KM.

Department of Veterinary Basic Sciences, The Royal Veterinary College, London, UK.

The influence of chylomicron remnants enriched in n-6 or n-3 polyunsaturated fatty acids (PUFA) on the expression of mRNA for the low density lipoprotein receptor (LDLr), LDLr-related protein (LRP), and peroxisome proliferator activated receptor alpha (PPAR(alpha)) was investigated in normal hepatocytes and after manipulation of the cellular oxidative state by incubation with N-acetyl cysteine (NAC) or CuSO(4). In normal cells, mRNA levels for the LDLr were unaffected by incubation with chylomicron remnants, but those for the LRP and PPAR(alpha) were downregulated by remnants enriched in n-3 as compared to n-6 PUFA, suggesting that the transcription of these genes are influenced directly by the type of fatty acid delivered to the liver from the diet. Treatment with NAC or CuSO(4) was found to shift the hepatocytes into a pro-reducing or pro-oxidizing state, respectively. The abundance of mRNA for the LDLr, LRP, and PPAR(alpha) was increased after incubation with remnants enriched in n-3, but not n-6, PUFA in pro-reducing as compared to pro-oxidizing cells, and PPAR(alpha) mRNA levels were also decreased by remnants high in n-6 PUFA in the more reduced cells. These results indicate that the effects of fatty acids from the diet delivered to the liver in chylomicron remnants on the expression of hepatic genes regulating their uptake and metabolism are modulated by the redox state of the cells, and that the type of fatty acid carried by the particles also plays a part in determining the response observed.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12031897&dopt=Abstract

Diabetes. 2002 Jun;51(6):1708-13.
Differential effects of fenofibrate or simvastatin treatment of rats on hepatic microsomal overt and latent diacylglycerol acyltransferase activities.

Waterman IJ, Zammit VA.

Cell Biochemistry, Hannah Research Institute, Ayr, Scotland.

Hepatic triacylglycerol secretion is elevated in insulin-resistant states. Microsomal diacylglycerol acyltransferase (DGAT) catalyzes the final reaction in the synthesis of triacylglycerol (TAG). We have previously described two DGAT activities in rat liver microsomes, one overt (cytosol-facing) and one latent (endoplasmic reticulum lumen-facing) (Owen MR, Corstorphine CG, Zammit VA: Overt and latent activities of diacylglycerol acytransferase in rat liver microsomes: possible roles in very-low-density lipoprotein triacylglycerol secretion. Biochem J 323:17-21, 1977). It was suggested that they are involved in the synthesis of TAG for the cytosolic droplet and VLDL lipidation, respectively. In the present study, we measured the overt and latent DGAT activities in rats fed diets containing one of two hypolipidemic drugs: fenofibrate (a peroxisome proliferator-activated receptor alpha [PPARalpha] agonist) and simvastatin (a 3-hydroxy-3-methylglutaryl [HMG]-CoA reductase inhibitor). We found that the activities of the two DGATs could be varied independently by these treatments. Fenofibrate raised overt DGAT activity but lowered that of latent DGAT. In contrast, simvastatin markedly lowered overt DGAT activity without affecting that of latent DGAT. The increase in overt DGAT activity induced by fenofibrate could not be mimicked by feeding a diet enriched in n-3 polyunsaturated fatty acids (PUFA), which lowered overt DGAT activity but did not affect latent DGAT, suggesting that n-3 PUFA act through a mechanism independent of PPARalpha activation. The fibrate-induced increase in overt DGAT activity and the inhibition of latent DGAT may provide a mechanism through which acyl moieties are retained within the liver for oxidation through the pathways concomitantly upregulated by PPARalpha activation.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12031956&dopt=Abstract

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