title: Heme oxygenase-1 plays an important protective role in experimental autoimmune encephalomyelitis.
abstract: Increasing evidence shows that oxidative stress plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of the human disease, multiple sclerosis (MS). Heme oxygenase-1 (HO-1) is a heat shock protein induced by oxidative stress. HO-1 metabolizes heme to the antioxidant bilirubin and carbon monoxide, and represents a powerful endogenous defensive mechanism against free radicals in many diseases. However, the role of this important enzyme in EAE remains unknown. In this study, we showed high expression of HO-1 in lesions of EAE, and demonstrated that hemin, an inducer of HO-1, inhibited EAE effectively. In contrast, tin mesoporphyrin, an inhibitor of HO-1, markedly exacerbated EAE. Our results suggest that endogenous HO-1 plays an important protective role in EAE, and that targeted induction of HO-1 overexpression may represent a new therapy for the treatment of multiple sclerosis.
authors: Brain Research Center, University of British Columbia, 2550 Willow Street, Vancouver, B.C. V5Z 3N9, Canada.
authors: Y
authors: Y
authors: Liu
authors: B
authors: B
authors: Zhu
authors: L
authors: L
authors: Luo
authors: P
authors: P
authors: Li
authors: D W
authors: DW
authors: Paty
authors: M S
authors: MS
authors: Cynader
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D018696:Neuroprotective Agents; C055421:tin mesoporphyrin; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1