ABSTRACT
Introduction 123
Cellular Viability in Response to Antioxidants 125
Expression of Apoptosis and Cell Survival-Related Genes and
Proteins in Response to Antioxidants 125
The Effect of the Antioxidants on Caspase-3 Protein Level and Activity 129
The Molecular Mechanism of Action of Antioxidants 134
Conclusion 137
Acknowledgment 137
References 137
INTRODUCTION
Parkinson’s disease (PD) is a progressive and age-dependent neurodegenerative
disease, characterized at cellular level by a depletion of dopamine (DA) in
DA neurons of substantia nigra pars compacta (SNPC). Although the etiology
of the neuronal cell death is still unclear and no casual therapy is available yet, the
current view supports oxidative stress (OS) as a key factor of neurodegeneration
(1,2). Analysis of Parkinsonian brain samples demonstrated certain apoptotic cell
features in DA neurons of SNPC, but the reported results remain highly
controversial (3). However, in vitro and in vivo experiments with neurotoxins
such as 6-hydroxydopamine (6-OHDA) (4) and N-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP) (5) have shown OS-dependent apoptosis in death
of DA neurons and many of the neurochemical changes reported in substantia
nigra of Parkinsonian brains (6), and thus it may be a contributing pathway to
dopaminergic neuronal cell death in PD (7). Previous studies have shown that
high concentrations of antioxidants, such as DA, DA D1-D2-receptor agonist,
R-apomorphine (R-APO), green tea polyphenol (2)-epigallocatechine-3-gallate (EGCG), and the pineal indoleamine hormone, melatonin, can be cytotoxic to
neuronal cells (8-12), raising the question whether long-term treatment with
these compounds will contribute to the degeneration of the dopaminergic
neurons of the substantia nigra in PD (13). Nonetheless, the few clinical
studies done with these compounds have not exhibited such a phenomenon.
Thus, the in vitro studies with these antioxidant agents are not compatible with
in vivo studies.
