Myelin basic protein induces heme oxygenase-1 in human astroglial cells.
Heme oxygenase-1 (HO-1), also known as heat-shock protein 32 (HSP-32), is induced in many cells by a large variety of stimuli. Its induction in nervous system cells following toxic and oxidative stress was suggested to play a protective role. Its presence was recently detected by immunohistochemical studies at the level of inflammatory lesions of rat experimental autoimmune encephalomyelitis. In the present study, we demonstrate that myelin basic protein (MBP) induces HO-1 in human astroglial cells, as shown by Western blots and RT-PCR. Proteolytic fragments derived from the whole MBP show a different behavior in the HO-1 induction: MBP152-167 was able to produce a light but still significant increase in HO-1 mRNA and protein levels, whereas MBP68-84 was not. The increase in HO-1 production seems to be mediated by a Ca(2+)-dependent mechanism, since MBP addition to astrocytoma cultures induced a strong and immediate increment of [Ca(2+)](i) increase; MBP152-167 elicited a delayed and less pronounced [Ca(2+)](i) increase; no [Ca(2+)](i) changes were induced following cell treatment with MBP68-84. NO pathway involvement in the induction of HO-1 by MBP was ruled out since the expression of the inducible isoform of nitric oxide synthase was not upregulated in treated cells, neither nitrite levels were modified, as demonstrated by Greiss reaction. The possible significance of HO-1 induction following MBP stimulation is discussed.
Businaro
Rita
R
Department of Cardiovascular Sciences, University "La Sapienza," Rome, Italy.
Fabrizi
Cinzia
C
Caronti
Brunella
B
Calderaro
Caterina
C
Fumagalli
Lorenzo
L
Lauro
Giuliana M
GM
D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D004660:Encephalitis / Q000201:enzymology* / Q000503:physiopathology; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000378:metabolism* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D002118:Calcium