Effect of Curcumin on Protein Damage Induced by Rotenone in Dopaminergic PC12 Cells

Abstract

Oxidative stress is considered to be a key factor of the pathogenesis of Parkinson’s disease, a multifactorial neurodegenerative disorder characterized by reduced dopaminergic neurons in the substantia nigra pars compacta and accumulated protein aggregates. Rotenone is a worldwide-used pesticide that induces the most common features of Parkinson’s by direct inhibition of the mitochondrial complex I. Rotenone-induced Parkinson’s models, as well as brain tissues from Parkinson’s patients, are characterized by the presence of both lipid peroxidation and protein oxidation markers resulting from the increased level of free radical species. Oxidation introduces several modifications in protein structure, including carbonylation and nitrotyrosine formation, which severely compromise cell function. Due to the link existing between oxidative stress and Parkinson’s disease, antioxidant molecules could represent possible therapeutic tools for this disease. In this study, we evaluated the effect of curcumin, a natural compound known for its antioxidant properties, in dopaminergic PC12 cells treated with rotenone, a cell model of Parkinsonism. Our results demonstrate that the treatment of PC12 cells with rotenone causes severe protein damage, with formation of both carbonylated and nitrotyrosine-derived proteins, whereas curcumin (10 µM) co-exposure exerts protective effects by reducing the levels of oxidized proteins. Curcumin also promotes proteasome activation, abolishing the inhibitory effect exerted by rotenone on this degradative system.

Obstacles against the Marketing of Curcumin as a Drug

“…Evidence in recent years supports the efficacy of curcumin in PD. In both in vitro and in vivo models of PD curcumin could prevent oxidative stress toxicity by reducing the production of ROS and malondialdehyde and restoring GSH levels [123][124][125] which shields against alpha-synuclein-induced toxicity in the brain [123]. More specifically, antioxidative and anti-apoptotic activity of curcumin has been reported in in vitro studies, indicating the neuroprotective effect of curcumin on dopaminergic neurons [124,125].…”

Dietary Antioxidants and Parkinson’s Disease

“…Curcumin scavenges biological radicals including superoxide anion, hydrogen peroxide, 1,1-diphenyl-2-picryl-hydrazyl free radical, 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) radical, and N , N -dimethyl- p -phenylenediamine dihydrochloride radical [ 205 ]. In addition, treatment with curcumin (10 μM) decreases oxidation-associated protein modification including carbonylation and nitrotyrosine formation to rescue dopaminergic cells [ 106 ]. Curcumin effectively protects mitochondria from oxidative stress-associated damage [ 206 ].…”

The pharmacological basis of the curcumin nutraceutical uses: an update

“…A new potential protective effect of curcumin on dopamine neurons is the regulation of autophagy, by decreasing the BAX/BCL2 ratio and increasing of LC3 and ATG10 expression (two factors involved in the formation of autophagosome) (273), by regulation of TFEB export signaling via inhibition of glycogen synthase kinase-3b (GSK-3b) (234), and by activation of autophagy in an ROS-dependent manner (255). Some authors demonstrated a key role of curcumin in reducing oxidative stress, for example lowering the level of ROS (274) and oxidized proteins (275), and through modulation of the NRF-2/HO-1 pathway (234). Furthermore, curcumin prevented the LPS-induced upregulation of the protein activity of NF-κB, proinflammatory cytokines (TNF-α, IL-1β, and IL-1α), and inducible nitric oxide synthase (iNOS).…”