Hypochlorite converts cysteinyl-dopamine into a cytotoxic product: A possible factor in Parkinson's Disease.
The dopamine oxidation product cysteinyl-dopamine has attracted attention as a contributor to the death of dopaminergic neurons in Parkinson's disease. Treatment of cysteinyl-dopamine with hypochlorite yields an even more cytotoxic product. This product has potent redox-cycling activity and initiates production of superoxide in PC12 cells. Taurine, which scavenges hypochlorite, protects PC12 cells from cysteinyl-dopamine but not from the hypochlorite product, suggesting that the product, not cysteinyl-dopamine itself, is toxic. Furthermore, rotenone, which enhances expression of the hypochlorite-producing enzyme myeloperoxidase, increases the cytotoxicity of cysteinyl-dopamine but not of the hypochlorite product. This suggests that dopamine oxidation to cysteinyl-dopamine followed by hypochlorite-dependent conversion to a cytotoxic redox-cycling product leads to the generation of reactive oxygen species and oxidative stress and may contribute to the death of dopaminergic neurons.
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States.
Nihar J
NJ
Mehta
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States.
Karam
K
Asmaro
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States.
David J
DJ
Hermiz
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States.
Meredith M
MM
Njus
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States.
Ashraf H
AH
Saleh
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States.
Karen A
KA
Beningo
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States. Electronic address: dnjus@wayne.edu.
David
D
Njus
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*
D003603:Cytotoxins; D013481:Superoxides; D013654:Taurine; D006997:Hypochlorous Acid; C047408:5-S-cysteinyldopamine; D009195:Peroxidase; D004298:Dopamine
Hypochlorite; Myeloperoxidase; Parkinson's disease; Redox cycling; Rotenone; Superoxide; Taurine