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.