917-96 In Vitro Inhibition of Smooth Muscle Cell Proliferation by Sterol 27-Hydroxylase Metabolites (original) (raw)
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Muscle & Nerve, 1988
L-carnitine stimulated CO2 production from 1-14C pyruvate in mitochondria from human skeletal muscle nearly twofold. A comparable increase in the pyruvate dehydrogenase complex (PDHC) activity was seen. Moreover, in the presence of L-carnitine and at pyruvate concentration greater than 0.25 mM, this effect was associated with a marked increase of acetylcarnitine synthesis. Deoxycarnitine, an inhibitor of carnitine acetyltransfersase (CAT), partially reversed the effect of carnitine on PDHC activity. The stimulatory effect of carnitine on PDHC activity in human mitochondria is mediated by the modulation of the intramitochondrial acetylCoA/CoASH ratio.
Biochemical Pharmacology, 1995
Thins study was designed to examine whether the depletion of L-carnitine may induce compensatory mechanisms allowing higher fatty acid oxidative activities in liver, particularly with regard to mitochondrial carnitine palmitoyltransferase I activity and peroxisomal fatty acid oxidation. Wistar rats received cl-carnitine for 2 days and 3-(2,2,2-trimethylhydrazinium)propionate (mildronate), a noncompetitive inhibitor of y-butyrobetaine hydroxylase, for 10 days. They were starved for 20 hr before being sacrificed. A dramatic reduction in carnitine concentration was observed in heart, skeletal muscles and kidneys, and to a lesser extent, in liver. Triacylglycerol content was found to be significantly more elevated on a gram liver and whole liver basis as well as per mL of blood (but to a lesser extent), while similar concentrations of ketone bodies were found in the blood of D-carnitine/mildronate-treated and control rats. In liver mitochondria, the specific activities of acyl-CoA synthetase and carnitine palmitoyltransferase I were enhanced by the treatment, while peroxisomal fatty acid oxidation was higher per gram of tissue. It is suggested that there may be an enhancement of cellular acyl-CoA concentration, a signal leading to increased liver fatty acid oxidation in acute carnitine deficiency.
Lipids, 1996
Recently, a new class of lipid lowering agents [3hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors] was introduced into clinical practice. The use of these agents could lead to a secondary deficiency in carnitine, which may manifest clinically as a myalgia/myositis--a side effect that is occasionally seen with this class of drugs. In the present study, we examined the effect of an HMG-CoA reductase inhibitor (Iovastatin) on serum and tissue levels of carnitine and carnitine acyltransferase activities in the rabbit. Rabbits (n = 6) were fed chow containing Iovastatin (30 rag/d) for 16 wk. Blood was collected and tissues (liver, heart, and skeletal muscle) harvested at sacrifice. Free and total carnitine were measured in serum and tissues by a radioenzymatic method. Carnitine acetyltransferase and carnitine palmitoyltransferase (CPT) activities were determined and expressed relative to DNA. Serum free (24.0 • 2.6 vs. 29.4 • 3.1 ~tM) and total (35.1 • 4.7 vs. 52.8 • 8.8 laM) carnitine levels increased significantly with 16 wk of treatment. This increase in total carnitine was mainly due to an increase in the levels of serum acylcamitine (12.7 + 3.1 vs 26.5 • 5.7 ~tM). Tissue levels of total carnitine were significantly decreased by the treatment. Carnitine acetyltransferase was unaffected by the treatment, whereas there was a significant increase in the activity of CPT in the liver and heart.
Effects of L-Carnitine and N-Acetylcysteine on nonalcoholic hepatic steatosis in rats
Medicine Science | International Medical Journal, 2019
This study was performed to investigate whether the antioxidants L-carnitine and N-acetylcysteine (NAC) have therapeutic effects on Nonalcoholic hepatic steatosis (NHS) in rats with carbon tetrachloride (CCl4)-induced fatty liver disease. Twenty-four healthy male and female Wistar Albino rats, weighing 220-250 g and obtained from our university health research institute, were used in this study. The animals were divided into four groups of six rats each: Group 1 [Diet + normal saline solution (NSS), control group], Group 2 [Diet + CCl4], Group 3 [Diet + CCl4 + L-carnitine] and Group 4 [Diet + CCl4 + NAC]. For biochemical examinations blood samples were obtained from the right ventricle of the heart and liver samples for histopathological were also obtained. The mean Aspartate aminotransferase (AST) (P = 0.043) and lactate dehydrogenase (LDH) levels (P=0.021) were significantly lower in rats with l-carnitine treatment. The mean ALT level were significantly lower in rats with NAC and (P = 0.014). Microscopic steatosis severity was decreased in the rats with NAC treatment than the controls. However administration of l-carnitine did not sufficiently prevent hepatic steatosis or inflammation. Our study showed that L-carnitine and NAC treatment resulted in significant regression of steatosis in rats with NHS. However, these findings must be confirmed by further studies including larger populations.
Stimulation of Non-oxidative Glucose Utilization by?-carnitine in Isolated Myocytes
Journal of Molecular and Cellular Cardiology, 1995
S. A-, M. S-A, M. A. N, S. C. H, J. S. L J. E. L. Stimulation of Non-oxidative Glucose Utilization by -carnitine in Isolated Myocytes. Journal of Molecular and Cellular Cardiology (1995) 27, 2465-2472. The effects of -carnitine on 14 CO 2 release from [1-14 C]pyruvate oxidation (an index of pyruvate dehydrogenase activity, PDH), [2-14 C]pyruvate, and [6-14 C]glucose oxidation (indices of the acetyl-CoA flux through citric acid cycle), and [U -14 C]glucose (an index of both PDH activity and the flux of acetyl-CoA through the citric acid cycle), were studied using isolated rat cardiac myocytes. -carnitine increased the release of 14 CO 2 from [1-14 C]pyruvate, and decreased that of [2-14 C]pyruvate in a time and concentration-dependent manner. At a concentration of 2.5 m, -carnitine produced a 50% increase of CO 2 release from [1-14 C]pyruvate and a 50% decrease from [2-14 C]pyruvate oxidation. -carnitine also increased CO 2 release from [1-14 C[pyruvate oxidation by 35%, and decreased that of [2-14 C]pyruvate oxidation 30%, in isolated rat heart mitochondria. The fatty acid oxidation inhibitor, etomoxir, stimulated the release of CO 2 from both [1-14 ]pyruvate and [2-14 C]pyruvate. These results were supported by the effects of -carnitine on the CO 2 release from [6-14 C]-and [U-14 C]glucose oxidation. -carnitine (5 m) decreased the CO 2 release from [6-14 C]glucose by 37%, while etomoxir (50 ) increased its release by 24%. -carnitine had no effect on the oxidation of [U-14 C]glucose. -carnitine increased palmitate oxidation in a time-and concentration-dependent manner in myocytes. Also, it increased the rate of efflux of acetylcarnitine generated from pyruvate in myocytes. These results suggest that -carnitine stimulates pyruvate dehydrogenase complex activity and enhances non-oxidative glucose metabolism by increasing the mitochondrial acetylcarnitine efflux in the absence of exogenous fatty acids.
Carnitine, mitochondrial function and therapy☆
Advanced Drug Delivery Reviews, 2009
Carnitine is important for cell function and survival primarily because of its involvement in the multiple equilibria between acylcarnitine and acyl-CoA esters established through the enzymatic activities of the family of carnitine acyltransferases. These have different acyl chain-length specificities and intracellular compartment distributions, and act in synchrony to regulate multiple aspects of metabolism, ranging from fuel-selection and -sensing, to the modulation of the signal transduction mechanisms involved in many homeostatic systems. This review aims to rationalise the extensive range of experimental and clinical data that have been obtained through the pharmacological use of L-carnitine and its short-chain acylesters, over the past two decades, in terms of the basic biochemical mechanisms involved in the effects of carnitine on the various cellular acyl-CoA pools in health and disease.
Fatty acid metabolism in hepatocytes cultured with hypolipidaemic drugs. Role of carnitine
Biochemical Journal, 1988
The direct effects of clofibrate analogues on carnitine acyltransferase activities and fatty acid metabolism were studied in cultured hepatocytes. Rat hepatocytes cultured with bezafibrate or ciprofibrate (0.1-10 micrograms/ml) for 48 h had increased activities of carnitine acetyltransferase (CAT; 4-6-fold) and carnitine palmitoyltransferase (CPT; 12-34%). The increase in CAT was higher in hepatocytes from the periportal zone (440%) of rat liver compared with cells from the perivenous zone (266%). In human hepatocytes, in contrast with rat, the fibrates did not cause a marked increase in CAT activity. The effects of fibrates on palmitate metabolism were dependent on the carnitine status. In the presence of exogenous carnitine (1 mM), rat hepatocytes cultured with bezafibrate had higher rates of total palmitate metabolism (29-34%) without increased partitioning of palmitate towards beta-oxidation, relative to control cultures. At low endogenous carnitine concentrations, cells culture...