Hypochlorite converts cysteinyl-dopamine into a cytotoxic product: A possible factor in Parkinson's Disease.
Title | Hypochlorite converts cysteinyl-dopamine into a cytotoxic product: A possible factor in Parkinson's Disease. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Mehta NJ, Asmaro K, Hermiz DJ, Njus MM, Saleh AH, Beningo KA, Njus D |
Journal | Free Radic Biol Med |
Volume | 101 |
Pagination | 44-52 |
Date Published | 2016 Dec |
ISSN | 1873-4596 |
Abstract | 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. |
DOI | 10.1016/j.freeradbiomed.2016.09.023 |
Alternate Journal | Free Radic. Biol. Med. |
PubMed ID | 27682361 |