The Effect of Heavy Metals on Nicotinamide \it{N}-methyltransferase Activity \it{In Vitro} Relating to Parkinson\rqs Disease

ABSTRACT

Objective: The aims of this study were to determine the effects of heavy metals such as manganese on nicotinamide N-methyltransferase (EC 2.1.1.1) (NNMT) activity and to consider the possibility of involvement of NNMT activation in the pathogenesis of heavy metal induced Parkinson’s disease. Methods: NNMT activity in supernatants separated from brain, liver and kidney homogenates of 5 elderly male Wistar rats by centrifugation were measured by high performance liquid chromatography system with fluorescence. NNMT activity under the conditon of 0.5 or 5.0 mM Mn2+, Fe2+, Cu2+ or Cd2+ was compared with control (no metal ion existence). Results: NNMT activities in rat brain, liver and kidneys were significantly decreased by Cu2+, and those in the liver and kidneys were significantly decreased by Cd2+. Mn2+ reduced NNMT activity only in the liver. Fe2+ had no effect on NNMT activity. Conclusions: No metal increased NNMT activity in this study, contrary to our hypothesis. Further study is needed to clarify the reason why the effects of Mn2+ and Fe2+ which have a high relevance to Parkinson’s disease on NNMT activity differ from those of Cu2+ and Cd2+.