Kainic acid induction of heme oxygenase in vivo and in vitro.
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.
Department of Neurobiology, Kyoto Pharmaceutical University, Yamashina, Japan.
Y
Y
Matsuoka
Y
Y
Kitamura
M
M
Okazaki
J
J
Kakimura
I
I
Tooyama
H
H
Kimura
T
T
Taniguchi
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D006419:Heme Oxygenase (Decyclizing); D007608:Kainic Acid