In vitro and in vivo induction of heme oxygenase-1 in rat glial cells: Possible involvement of nitric oxide production from inducible nitric oxide synthase

✍ Scribed by Yoshihisa Kitamura; Muneki Furukawa; Yasuji Matsuoka; Ikuo Tooyama; Hiroshi Kimura; Yasuyuki Nomura; Takashi Taniguchi

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 552 KB
• Volume: 22
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/(sici)1098-1136(199802)22:2<138::aid-glia5>3.0.co;2-3

✦ Synopsis

To determine whether heme oxygenase-1 (HO-1) protein is induced by endogenous nitric oxide (NO) in rat glial cultures, we examined the effects of lipopolysaccharide (LPS), interferon-␥ (IFN-␥), and NO donors such as S-nitroso-N-acetylpenicillamine (SNAP), in mixed glial cells and in vivo rat hippocampus. In cultured glial cells, treatment with LPS induced the expression of 130-kd inducible NO synthase (iNOS) after 6 h, and NO 2 Ϫ accumulation and enhancement of the protein level of 33-kd HO-1 after 12 h. In addition, treatment with SNAP induced HO-1 expression after 6 h. Although NOS inhibitors such as N G -nitro-L-arginine (NNA) and N G -methyl-L-arginine did not change LPS-induced iNOS expression, these inhibitors suppressed both NO 2 Ϫ accumulation and the enhancement of HO-1. Immunocytochemistry showed that treatment with LPS for 24 h induced iNOS immunoreactivity predominantly in ameboid microglia, while this treatment induced HO-1-immunoreactivity in both microglia and astrocytes. In in vivo rat hippocampus, microinjection of LPS plus IFN-␥, or SNAP after 24 h also induced HO-1 immunoreactivity in reactive microglia and astrocytes. In addition, intraperitoneal administration of NNA inhibited HO-1 immunoreactivity induced by the microinjection of LPS plus IFN-␥. These results suggest that endogenous NO production by iNOS in microglia causes autocrine and paracrine induction of HO-1 protein in microglia and astrocytes in vitro and in rat brain.