Neuroprotective role of heme-oxygenase 1 against iodoacetate-induced toxicity in rat cerebellar granule neurons: Role of bilirubin.
Heme oxygenase (HO) catalyses the breakdown of heme to iron, carbon monoxide and biliverdin, the latter being further reduced to bilirubin. A protective role of the inducible isoform, HO-1, has been described in pathological conditions associated with the production of reactive oxygen species (ROS). The aim of this study was to investigate the role of HO-1 in the neurotoxicity induced by iodoacetate (IAA) in primary cultures of cerebellar granule neurons (CGNs). IAA, an inhibitor of the glycolysis pathway, reduces cell survival, increases ROS production and enhances HO-1 expression in CGNs. Furthermore, the induction of HO-1 expression by cobalt protoporphyrin (CoPP) prevented cell death and ROS production induced by IAA, whereas the inhibition of HO activity with tin mesoporphyrin exacerbated the IAA-induced neurotoxicity. The protective effect elicited by CoPP was reproduced by bilirubin addition, suggesting that this molecule may be involved in the protective effect of HO-1 induction in this experimental model.
González-Reyes
Susana
S
Departamento de Biologia, Universidad Nacional Autonoma de Mexico, DF, Mexico.
Orozco-Ibarra
Marisol
M
Guzmán-Beltrán
Silvia
S
Molina-Jijón
Eduardo
E
Massieu
Lourdes
L
Pedraza-Chaverri
José
J
D000818:Animals; D001663:Bilirubin / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D002526:Cerebellar Diseases / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004790:Enzyme Induction; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D019807:Iodoacetic Acid / Q000633:toxicity*; D008665:Metalloporphyrins / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011913:Rats, Inbred BB; D017382:Reactive Oxygen Species / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
D008665:Metalloporphyrins; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D014404:Tubulin; C055421:tin mesoporphyrin; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1; D001663:Bilirubin; D019807:Iodoacetic Acid