Inhibitory effects of pesticides on proteasome activity: Implication in Parkinson's disease

Xue-Feng Wang; Sharon Li; Arthur P. Chou; Jeff M. Bronstein

Neurobiology of Disease (Jul 2006)

Inhibitory effects of pesticides on proteasome activity: Implication in Parkinson's disease

Xue-Feng Wang,
Sharon Li,
Arthur P. Chou,
Jeff M. Bronstein

Affiliations

Xue-Feng Wang: Department of Neurology, University of California at Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA
Sharon Li: Department of Neurology, University of California at Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA
Arthur P. Chou: Department of Neurology, University of California at Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA
Jeff M. Bronstein: Department of Neurology, University of California at Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA; The Greater Los Angeles Veterans Administration Medical Center, Los Angeles, CA 90073, USA; Corresponding author. Department of Neurology, UCLA David Geffen School of Medicine, Reed Neurological Research Center, 710 Westwood Plaza, A-153, Los Angeles, CA 90095, USA. Fax: +1 310 206 9819.

Journal volume & issue: Vol. 23, no. 1
pp. 198 – 205

Abstract

Read online

Epidemiological studies have suggested a correlation of pesticides and Parkinson's disease (PD) while genetic and biochemical studies have implicated the ubiquitin–proteasome system (UPS) in the pathogenesis of PD. In the present studies, we tested the hypothesis that pesticide exposure increases the risk of developing PD by inhibiting the UPS. The effects of pesticides on proteasome activity were examined in SK-N-MC neuroblastoma cells overexpressing a GFP-conjugated proteasome degradation signal, GFPu. Six out of 25 representative pesticides, including rotenone, ziram, diethyldithiocarbamate, endosulfan, benomyl, and dieldrin, showed inhibitory effects on proteasome activities at low concentrations (10 nM to 10 μM). Unlike proteasome inhibitors, they did not inhibit 20 S proteasome activities in cell lysates. Except for rotenone, the other five pesticides did not induce significantly cellular oxidative stress. The cytotoxic effects of these pesticides were closely correlated with proteasome inhibition. Our results suggest proteasome inhibition as a potential mechanism for the epidemiological association of pesticides and PD.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

About the journal

Abstract

Keywords