Neuroprotective role of heme-oxygenase 1 against iodoacetate-induced toxicity in rat cerebellar granule neurons: Role of bilirubin.

Full 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.

Author information

Author/s: González-Reyes, Susana (S); Orozco-Ibarra, Marisol (M); Guzmán-Beltrán, Silvia (S); Molina-Jijón, Eduardo (E); Massieu, Lourdes (L); Pedraza-Chaverri, José (J);

Affiliation: Departamento de Biologia, Universidad Nacional Autonoma de Mexico, DF, Mexico.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Free radical research (Free Radic Res), published in England. (Language: eng)

Reference: 2009-Mar; vol 43 (issue 3) : pp 214-23

Dates: Created 2009/02/24; Completed 2009/08/24;

PMID: 19177228, status: MEDLINE (last retrieved date: 8/24/2009)

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals
Bilirubin - metabolism; pharmacology
Blotting, Western
Cerebellar Diseases - chemically induced; enzymology; prevention & control
Cerebellum - cytology; drug effects; enzymology
Enzyme Induction
Heme Oxygenase-1 - antagonists & inhibitors; biosynthesis; metabolism
Iodoacetic Acid - toxicity

Iodoacetic Acid - toxicity
Metalloporphyrins - pharmacology
Neurons - drug effects; enzymology; metabolism
Protoporphyrins - pharmacology
Rats
Rats, Inbred BB
Reactive Oxygen Species - metabolism
Tubulin - metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Metalloporphyrins (0) ; Protoporphyrins (0) ; Reactive Oxygen Species (0) ; Tubulin (0) ; tin mesoporphyrin (106344-20-1) ; cobaltiprotoporphyrin (14325-03-2) ; Bilirubin (635-65-4) ; Iodoacetic Acid (64-69-7) ; Heme Oxygenase-1 (EC 1.14.99.3)

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