Curcumin pretreatment induces Nrf2 and an antioxidant response and prevents hemin-induced toxicity in primary cultures of cerebellar granule neurons of rats.
Curcumin is a bifunctional antioxidant derived from Curcuma longa. This study identifies curcumin as a neuroprotectant against hemin-induced damage in primary cultures of cerebellar granule neurons (CGNs) of rats. Hemin, the oxidized form of heme, is a highly reactive compound that induces cellular injury. Pretreatment of CGNs with 5-30 μM curcumin effectively increased by 2.3-4.9 fold heme oxygenase-1 (HO-1) expression and by 5.6-14.3-fold glutathione (GSH) levels. Moreover, 15 μM curcumin attenuated by 55% the increase in reactive oxygen species (ROS) production, by 94% the reduction of GSH/glutathione disulfide (GSSG) ratio, and by 49% the cell death induced by hemin. The inhibition of heme oxygenase system or GSH synthesis with tin mesoporphyrin and buthionine sulfoximine, respectively, suppressed the protective effect of curcumin against hemin-induced toxicity. These data strongly suggest that HO-1 and GSH play a major role in the protective effect of curcumin. Furthermore, it was found that 24 h of incubation with curcumin increases by 1.4-, 2.3-, and 5.2-fold the activity of glutathione reductase, glutathione S-transferase and superoxide dismutase, respectively. Additionally, it was found that curcumin was capable of inducing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus. These data suggest that the pretreatment with curcumin induces Nrf2 and an antioxidant response that may play an important role in the protective effect of this antioxidant against hemin-induced neuronal death.
Departamento de Biología, Facultad de Química, Edificio F, Segundo Piso, Laboratorio 209, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, 04510 México, DF, Mexico.
Susana
S
González-Reyes
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas," 14080 Tlalpan, México, DF, Mexico.
Silvia
S
Guzmán-Beltrán
Departamento de Biología, Facultad de Química, Edificio F, Segundo Piso, Laboratorio 209, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, 04510 México, DF, Mexico.
Omar Noel
ON
Medina-Campos
Departamento de Biología, Facultad de Química, Edificio F, Segundo Piso, Laboratorio 209, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, 04510 México, DF, Mexico.
José
J
Pedraza-Chaverri
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects; D019803:Glutathione Disulfide / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006427:Hemin / Q000633:toxicity*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D020011:Protective Agents; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D017382:Reactive Oxygen Species; D006427:Hemin; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D003474:Curcumin; D019803:Glutathione Disulfide