Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kainic acid-induced seizures in the rat brain cause severe brain damage that is thought to result, in part, from oxidative stress. In this study, we examine the consequences of systemic administration of kainic acid on expression of several genes that encode proteins thought to play roles in protection from oxidative stress, including metallothionein-I, and -III. Kainic acid causes an increase in metallothionein-I and heme oxygenase-I mRNAs, as well as an increase in c-fos, heat shock protein-70, and interleukin-1 beta mRNAs. The induction of these mRNAs is seizure dependent, and is greater in brain areas with extensive damage (e.g. piriform cortex) than in areas with minimal damage (e.g. frontal cortex and cerebellum). In contrast, little or no change in mRNA for metallothionein-III, manganese superoxide dismutase, copper-zinc superoxide dismutase, glutathione-s-transferase ya subunit or glutathione peroxidase occur. The prolonged and robust concordant induction of the metallothionein-I and heme oxygenase-I genes may reflect the oxidative stress produced by kainic acid-induced seizures. In addition, the induction of interleukin-1 beta gene expression suggests an inflammatory response in brain regions damaged by kainic acid-induced seizures. Delineating the regulation of genes associated with oxidative and inflammatory responses can contribute to a fuller understanding of seizures and associated brain damage.
 ...
PMID:Temporalspatial patterns of expression of metallothionein-I and -III and other stress related genes in rat brain after kainic acid-induced seizures. 765 48

Heme oxygenase, catalyses oxidation of the heme molecule in concert with NADPH-cytochrome P450 reductase and then specifically cleaves heme into biliverdin, carbon monoxide, and iron. Biliverdin and its product, bilirubin, are known to be strong antioxidants. Kainic acid is a potent neurotoxin, and induces selective neuronal loss in the rat hippocampus. Kainic acid acts on the kainate receptors, and kainic acid neurotoxicity may be in part mediated by oxidative stress. In this study, we examined whether or not heme oxygenase was activated in kainic acid-induced neurotoxicity. After intracerebroventricular injection of kainic acid, the heme oxygenase-1 protein level was strongly enhanced, although the constitutive heme oxygenase (heme oxygenase-2) protein level was not changed. One day after treatment, the protein level of heme oxygenase-1 reached a maximum and then gradually decreased over a period of three to seven days. In the rat hippocampus, cells expressing heme oxygenase-1 in vivo were predominately microglia and only a few astrocytes. In addition, heme oxygenase-1 immunoreactivity was predominantly co-localized with major histocompatibility complex class II-, and partly co-localized with class I-immunoreactive microglia. In cultured glial cells in vitro, heme oxygenase- protein was expressed in the microglia even with the vehicle treatment, and was strongly induced in astrocytes by kainic acid treatment. These results suggest that ameboid microglia, which express both heme oxygenase-1 and major histocompatibility complex antigens, may play a key role in a delayed episode of kainic acid-induced microglial activation and neurodegeneration.
 ...
PMID:Kainic acid induction of heme oxygenase in vivo and in vitro. 968 59