The Harman and Norharman Reduced Dopamine Content and Induced Cytotoxicity in PC12 Cells

Abstract

The effects of harman and norharman on dopamine content and L-DOPA-induced cytotoxicity were investigated in PC12 cells. Harman and norharman decreased the intracellular dopamine content for 24 h. The <TEX>$IC_{50}$</TEX> values of harman and norharman were 20.4 <TEX>${\mu}M$</TEX> and 95.8 <TEX>${\mu}M$</TEX>, respectively. Tyrosine hydroxylase (TH) activity and TH mRNA levels were also decreased by 20 <TEX>${\mu}M$</TEX> harman and 100 <TEX>${\mu}M$</TEX> norharman. Under the same conditions, the intracellular cyclic AMP levels were decreased by harman and norharman. In addition, harman and norharman at concentrations higher than 80 <TEX>${\mu}M$</TEX> and 150 <TEX>${\mu}M$</TEX> caused cytotoxicity at 24 h in PC12 cells. Non-cytotoxic ranges of 10-30 <TEX>${\mu}M$</TEX> harman and 50-150 <TEX>${\mu}M$</TEX> norharman inhibited L-DOPA (20-50 <TEX>${\mu}M$</TEX>)-induced increases of dopamine content at 24 h. Harman at 20-150 <TEX>${\mu}M$</TEX> and norharman at 100-300 <TEX>${\mu}M$</TEX> also enhanced LDOPA (20-100 <TEX>${\mu}M$</TEX>)-induced cytotoxicity at 24 h. These results suggest that harman and norharman decrease dopamine content by reducing TH activity and aggravate L-DOPA-induced cytotoxicity in PC12 cells.