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PMID:19177228

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Citation

González-Reyes, S, Orozco-Ibarra, M, Guzmán-Beltrán, S, Molina-Jijón, E, Massieu, L and Pedraza-Chaverri, J (2009) Neuroprotective role of heme-oxygenase 1 against iodoacetate-induced toxicity in rat cerebellar granule neurons: Role of bilirubin. Free Radic. Res. 43:214-23

Abstract

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.

Links

PubMed Online version:10.1080/10715760802676670

Keywords

Animals; Bilirubin/metabolism; Bilirubin/pharmacology; Blotting, Western; Cerebellar Diseases/chemically induced; Cerebellar Diseases/enzymology; Cerebellar Diseases/prevention & control; Cerebellum/cytology; Cerebellum/drug effects; Cerebellum/enzymology; Enzyme Induction; Heme Oxygenase-1/antagonists & inhibitors; Heme Oxygenase-1/biosynthesis; Heme Oxygenase-1/metabolism; Iodoacetic Acid/toxicity; Metalloporphyrins/pharmacology; Neurons/drug effects; Neurons/enzymology; Neurons/metabolism; Protoporphyrins/pharmacology; Rats; Rats, Inbred BB; Reactive Oxygen Species/metabolism; Tubulin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:HMOX1

involved_in

GO:0043524: negative regulation of neuron apoptotic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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