The effect of heavy metals on nicotinamideN-methyltransferase activityin vitro relating to Parkinson's disease

ABSTRACT

<p><b>OBJECTIVE</b>The aims of this study were to determine the effects of heavy metals such as manganese on nicotinamideN-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.</p><p><b>METHODS</b>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 Mn(2+), Fe(2+), Cu(2+) or Cd(2+) was compared with control (no metal ion existence).</p><p><b>RESULTS</b>NNMT activities in rat brain, liver and kidneys were significantly decreased by Cu(2+), and those in the liver and kidneys were significantly decreased by Cd(2+). Mn(2+) reduced NNMT activity only in the liver. Fe(2+) had no effect on NNMT activity.</p><p><b>CONCLUSIONS</b>No metal increased NNMT activity in this study, contrary to our hypothesis. Further study is needed to clarify the reason why the effects of Mn(2+) and Fe(2+) which have a high relevance to Parkinson's disease on NNMT activity differ from those of Cu(2+) and Cd(2+).</p>