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The effect of endogenous dopamine in rotenone-induced toxicity in PC12 cells

Dukes, AA and Korwek, KM and Hastings, TG (2005) The effect of endogenous dopamine in rotenone-induced toxicity in PC12 cells. Antioxidants and Redox Signaling, 7 (5-6). 630 - 638. ISSN 1523-0864

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Deficiencies in Complex I have been observed in Parkinson's disease (PD) patients. Systemic exposure to rotenone, a Complex I inhibitor, has been shown to lead to selective dopaminergic cell death in vivo and toxicity in many in vitro models, including dopaminergic cell cultures. However, it remains unclear why rotenone seems to affect dopaminergic cells more adversely. Therefore, the role of dopamine (DA) in rotenone-induced PC12 cell toxicity was examined. Rotenone (1.0 μM) caused significant toxicity in differentiated PC12 cells, which was accompanied by decreases in ATP levels, changes in catechol levels, and increased DA oxidation. To determine whether endogenous DA makes PC12 cells more susceptible to rotenone, cells were treated with the tyrosine hydroxylase inhibitor α-methyl-p-tyrosine (AMPT) to reduce DA levels prior to rotenone exposure, and then cell viability was measured. No changes in rotenone-induced toxicity were observed with or without AMPT treatment. However, a potentiation of toxicity was observed following coexposure of PC12 cells to rotenone and methamphetamine. To determine whether this effect was due to DA, PC12 cells were depleted of DA prior to methamphetamine and rotenone cotreatment, resulting in a large attenuation in toxicity. These findings suggest that DA plays a role in rotenone-induced toxicity and possibly the vulnerability of DA neurons in PD.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Dukes, AA
Korwek, KM
Hastings, TGthasting@pitt.eduTHASTING
Date: 1 May 2005
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: Antioxidants and Redox Signaling
Volume: 7
Number: 5-6
Page Range: 630 - 638
DOI or Unique Handle: 10.1089/ars.2005.7.630
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Refereed: Yes
ISSN: 1523-0864
Date Deposited: 18 Apr 2014 16:27
Last Modified: 02 Feb 2019 16:56


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