L-Carnitine alters nitric oxide synthase activity in fibroblasts depending on the peroxisomal status.
Fibroblast cellular models are widely used for research on fatty acid metabolism. Due to the importance of L-carnitine in intermediary metabolism we studied the effects of L-carnitine on healthy human skin fibroblasts and fibroblasts without functional peroxisomes (Zellweger Syndrome) cultivated under carnitine deficiency, which is caused by standard media compositions. The application of physiological (0.1mM) or super-physiological (1mM) doses of L-carnitine causes a significant decrease of the specific activity of nitric oxide synthase (NOS, 2.25+/-0.10 to 1.36 pmol/(minmg)+/-0.09 pmol/(minmg) at 0.1mM), proliferation and a tendentious decrease of the antioxidant defence potential against hydrogen peroxide only in control cells. Simultaneous application of L-carnitine and 100 micro M N-acetylcysteine (NAC) prevents the alterations in control cells. Thus, L-carnitine alters the cellular regulation of the NOS probably by reactive oxygen species (ROS), which suggests that carnitine deficient media neither reflect physiological conditions for cellular models for fatty acid metabolism nor for the regulation of NOS.
Koeck
Thomas
T
Department of Medical Chemistry, School of Medicine, University of Vienna, Waehringerstrasse 10, Vienna A-1090, Austria.
Kremser
Karl
K
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D002331:Carnitine / Q000172:deficiency / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D005227:Fatty Acids / Q000032:analysis / Q000097:blood; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D018675:Toxicity Tests; D015211:Zellweger Syndrome / Q000473:pathology
D000975:Antioxidants; D005227:Fatty Acids; D011506:Proteins; D006861:Hydrogen Peroxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D002331:Carnitine; D000111:Acetylcysteine