Heme oxygenase-1 in SJL mice with experimental allergic encephalomyelitis.
The expression of heme oxygenase-1 (HO-1) is increased in the CNS of mice and rats with experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). To investigate the role of HO-1 in EAE, a putative inhibitor [tin-protoporphyrin IX (Sn-PP IX)] of HO-1 was administered to SJL mice during active disease. Sn-PP IX (200 micromol/kg) attenuated clinical scores, weight loss, and some signs of pathology in comparison to vehicle treatment. Glutathione levels were greater in treated EAE mice than in those receiving vehicle, indicating lower oxidative stress in the former group. These data suggest that inhibition of HO-1 attenuated disease and suppressed free radical production. In the SJL model of EAE, extravasated blood is present in the CNS, and iron released by HO-1 from this heme source may not be adequately sequestered by ferritin, allowing for iron-mediated tissue damage. Thus, HO-1 may act to amplify the disease process in this model.
Chakrabarty
A
A
Department of Molecular and Integrative Physiology, Mental Retardation and Human Development Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Emerson
M R
MR
LeVine
S M
SM
D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005293:Ferritins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism; D037102:Lectins; D008565:Membrane Proteins; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D004676:Myelin Basic Protein / Q000032:analysis; D009413:Nerve Fibers, Myelinated / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress; D011524:Protoporphyrins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology
D004791:Enzyme Inhibitors; D037102:Lectins; D008565:Membrane Proteins; D008665:Metalloporphyrins; D004676:Myelin Basic Protein; D011524:Protoporphyrins; D005293:Ferritins; C032628:tin protoporphyrin IX; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D005978:Glutathione