title: Quercetin and sesamin protect neuronal PC12 cells from high-glucose-induced oxidation, nitrosative stress, and apoptosis.
abstract: Complications of diabetes are now well-known to affect sensory, motor, and autonomic nerves. Diabetes is also thought to be involved in neurodegenerative processes characteristic of several neurodegenerative diseases. Indeed, it has been acknowledged recently that hyperglycemia-induced oxidative stress contributes to numerous cellular reactions typical of central nervous system deterioration. The goal of the present study was to evaluate the effects of the polyphenol quercetin and the lignan sesamin on high-glucose (HG)-induced oxidative damage in an in vitro model of dopaminergic neurons, neuronal PC12 cells. When incubated with HG (13.5 mg/mL), neuronal PC12 cells showed a significant increase of cellular death. Our results revealed that quercetin and sesamin defend neuronal PC12 cells from HG-induced cellular demise. An elevated level of reactive oxygen and nitrogen species is a consequence of improved oxidative stress after HG administration, and we demonstrated that this production diminishes with quercetin and sesamin treatment. We also found that quercetin and sesamin elicited an increment of superoxide dismutase activity. DNA fragmentation, Bax/Bcl-2 ratio, nuclear translocation of apoptosis-inducing factor, as well as poly(adenosine diphosphate [ADP]-ribose) polymerase cleavage were significantly reduced by quercetin and sesamin administration, affirming their antiapoptotic features. Also, HG treatment impacted caspase-3 cleavage, supporting caspase-3-dependent pathways as mechanisms of apoptotic death. Our results indicate a powerful role for these natural dietary compounds and emphasize preventive or complementary nutritional strategies for diabetes control.
authors.affiliation: Cellular Neurobiology, Department of Biochemistry, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Bournival
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Francoeur
authors.forename: Justine
authors.initials: J
authors.lastname: Renaud
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Martinoli
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D004149:Dioxoles / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005609:Free Radicals / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000633:toxicity*; D017705:Lignans / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D015538:Nitrosation / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D016716:PC12 Cells; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D013312:Stress, Physiological / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D004149:Dioxoles; D005609:Free Radicals; D017705:Lignans; D020011:Protective Agents; D011794:Quercetin; D013482:Superoxide Dismutase; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D005947:Glucose; C054125:sesamin