Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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The Harman and Norharman Reduced Dopamine Content and Induced Cytotoxicity in PC12 Cells

  • Yang, Yoo-Jung (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Lim, Sung-Cil (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Lee, Myung-Koo (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University)
  • Published : 2008.06.30
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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 $IC_{50}$ values of harman and norharman were 20.4 ${\mu}M$ and 95.8 ${\mu}M$, respectively. Tyrosine hydroxylase (TH) activity and TH mRNA levels were also decreased by 20 ${\mu}M$ harman and 100 ${\mu}M$ 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 ${\mu}M$ and 150 ${\mu}M$ caused cytotoxicity at 24 h in PC12 cells. Non-cytotoxic ranges of 10-30 ${\mu}M$ harman and 50-150 ${\mu}M$ norharman inhibited L-DOPA (20-50 ${\mu}M$)-induced increases of dopamine content at 24 h. Harman at 20-150 ${\mu}M$ and norharman at 100-300 ${\mu}M$ also enhanced LDOPA (20-100 ${\mu}M$)-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.

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References

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