Sesamin modulates tyrosine hydroxylase, superoxide dismutase, catalase, inducible NO synthase and interleukin-6 expression in dopaminergic cells under MPP+-induced oxidative stress.

Oxidative stress is regarded as a mediator of nerve cell death in several neurodegenerative disorders, such as Parkinson's disease. Sesamin, a lignan mainly found in sesame oil, is currently under study for its anti-oxidative and possible neuroprotective properties. We used 1-methyl-4-phenyl-pyridine (MPP(+)) ion, the active metabolite of the potent parkinsonism-causing toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, to produce oxidative stress and neurodegeneration in neuronal PC12 cells, which express dopamine, as well as neurofilaments. Our results show that picomolar doses of sesamin protected neuronal PC12 cells from MPP(+)-induced cellular death, as revealed by colorimetric measurements and production of reactive oxygen species. We also demonstrated that sesamin acted by rescuing tyrosine hydroxylase levels from MPP(+)-induced depletion. Sesamin, however, did not modulate dopamine transporter levels, and estrogen receptor-alpha and -beta protein expression. By examining several parameters of cell distress, we found that sesamin also elicited a strong increase in superoxide dismutase activity as well as protein expression and decreased catalase activity and the MPP(+) stimulated inducible nitric oxide synthase protein expression, in neuronal PC12 cells. Finally, sesamin possessed significant anti-inflammatory properties, as disclosed by its potential to reduce MPP(+)-induced interleukin-6 mRNA levels in microglia. From these studies, we determined the importance of the lignan sesamin as a neuroprotective molecule and its possible role in complementary and/or preventive therapies of neurodegenerative diseases.

Oxidative stress and 17-alpha- and 17-beta-estradiol modulate neurofilaments differently.

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). Neuronal death in the substantia nigra of PD patients is partly caused by exacerbated oxidative damage. Our previous studies demonstrated that oxidative stress can alter the structure and stability of neurofilament (NF) proteins and that 17-alpha- and 17-beta-estradiol are potent neuroprotective agents. The aim of this study was to investigate the cytoskeletal target of neuroprotection by estrogens in neuronal PC12 cells. We induced oxidative stress by MPP+ administration for 24 h, and 17-alpha- and 17-beta-estradiol were used as neuroprotective drugs. We measured gene expression and protein expression of each NF subunit, NFL, NFM, and NFH, by semiquantitative RT-PCR, Western blot, and immunofluorescence. Our results demonstrate that NFL mRNA and protein levels are not modulated by MPP+ or estradiol isomers, whereas NFM gene expression, as well as protein expression, are strongly influenced by MPP+, 17-alpha-, and 17-beta-estradiol after a 24-h treatment. Finally, mRNA levels of the most phosphorylated subunits, NFH, are not changed by MPP+ or treatment with both estradiol isomers, whereas NFH protein expression is decreased by the same treatments. These results suggest that oxidative stress affects neuronal cytoskeleton, maybe though proteolysis and/or abnormal structural changes in NFs. Then, 17-alpha- and 17-beta-estradiol might help the neuronal cell in recovering after oxidative stress by inducing protein expression of NFM and NFH subunits.