ABSTRACT
Title
Natural-like curcumin derivatives protect PC12 cells against Mn, MPP+ and H2O2 damage
Authors
S. Dedola1, D. Fabbri2, M.A. Dettori2, G. Delogu2, P. Ruzza2, P.A. Serra1, M.S. Desole1, R. Migheli1
1 Dept. of Neuroscience, University of Sassari, Italy
2 Instituteof Biomolecular Chemistry of CNR, Sassari and Padua Units, Italy
1 Dept. of Neuroscience, University of Sassari, Italy
2 Instituteof Biomolecular Chemistry of CNR, Sassari and Padua Units, Italy
Abstract
Parkinson's disease (PD) affects 1% of the population over the age of 65 and is the second most common progressive neurodegenerative disorder after Alzheimer's disease (AD).The classical symptoms of PD include resting tremor, muscular rigidity and bradykinesia resulting from the progressive loss of dopaminergic neurons in the substantia nigra (Wang et al., 2010).
Oxidative stress caused by mitochondrial dysfunction and the oxidative metabolism of dopamine play an important role in the pathogenesis of PD. The dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), has been widely used as an inducer of animal models of PD while manganese neurotoxicity results in Parkinson-like symptoms associated with the generation of reactive oxygen species. Hydrogen peroxide (H2O2) easily damages biological molecules, resulting in apoptotic or necrotic cell death. H2O2 has been extensively used as an inducer of oxidative stress in vitro models. The rat pheochromocytoma cell line PC12 has been used as a dopaminergic cell model for PD research.
With the aim to evaluate the capability of new curcumin-related compound to act as lead compounds in the development of innovative therapeutic approach in the PD, we investigated their potential neuroprotection against different models of oxidative stress.Therefore, inhibition of oxidative damage by supplementation of antioxidants becomes an attractive therapeutic strategy to reduce the risk of PD.Curcumin is a naturally occurring phenolic compound isolated as a yellow pigment from turmeric (dry rhizomes of Curcuma longa) which is commonly used as a spice and food colorant. This compound has attracted considerable attention due to its various biological and pharmacological activities, including antioxidant, and anticancer activities (Dai et al., 2009). A new family of natural-like curcumin derivatives has been synthesised and tested in vitro. In order to study the potential protective effects ofnew curcumin-related compound, PC12 cells were preincubated for 20’ with each antioxidant molecule then exposed to increasing concentrations of MPP+, MnCl2 and H2O2 for 24 h. All experiments were performed on PC12 cells during their exponential phase of growth. For each experiment 1x105 cells/ml were plated and treated 24 h later (time 0). The cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay (Migheli et al.1999). Preliminary results show that the curcumin and its natural-like derivatives protect PC12 cells against Mn- and MPP+-induced cytotoxicity and H2O2-induced oxidative stress and suggest the potential introduction of some of these molecules in PD therapy.
Wang et al. (2010). BMC Neuroscience11: 57.
Dai et al. (2009). Phitotherapy Research 23: 1220-1228.
Migheli et al. (1999). Journal of Neurochemistry 73: 1155-1163.
Oxidative stress caused by mitochondrial dysfunction and the oxidative metabolism of dopamine play an important role in the pathogenesis of PD. The dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), has been widely used as an inducer of animal models of PD while manganese neurotoxicity results in Parkinson-like symptoms associated with the generation of reactive oxygen species. Hydrogen peroxide (H2O2) easily damages biological molecules, resulting in apoptotic or necrotic cell death. H2O2 has been extensively used as an inducer of oxidative stress in vitro models. The rat pheochromocytoma cell line PC12 has been used as a dopaminergic cell model for PD research.
With the aim to evaluate the capability of new curcumin-related compound to act as lead compounds in the development of innovative therapeutic approach in the PD, we investigated their potential neuroprotection against different models of oxidative stress.Therefore, inhibition of oxidative damage by supplementation of antioxidants becomes an attractive therapeutic strategy to reduce the risk of PD.Curcumin is a naturally occurring phenolic compound isolated as a yellow pigment from turmeric (dry rhizomes of Curcuma longa) which is commonly used as a spice and food colorant. This compound has attracted considerable attention due to its various biological and pharmacological activities, including antioxidant, and anticancer activities (Dai et al., 2009). A new family of natural-like curcumin derivatives has been synthesised and tested in vitro. In order to study the potential protective effects ofnew curcumin-related compound, PC12 cells were preincubated for 20’ with each antioxidant molecule then exposed to increasing concentrations of MPP+, MnCl2 and H2O2 for 24 h. All experiments were performed on PC12 cells during their exponential phase of growth. For each experiment 1x105 cells/ml were plated and treated 24 h later (time 0). The cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay (Migheli et al.1999). Preliminary results show that the curcumin and its natural-like derivatives protect PC12 cells against Mn- and MPP+-induced cytotoxicity and H2O2-induced oxidative stress and suggest the potential introduction of some of these molecules in PD therapy.
Wang et al. (2010). BMC Neuroscience11: 57.
Dai et al. (2009). Phitotherapy Research 23: 1220-1228.
Migheli et al. (1999). Journal of Neurochemistry 73: 1155-1163.