PMID- 10792435 OWN - NLM STAT- MEDLINE DCOM- 20000724 LR - 20191210 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 12 IP - 5 DP - 2000 May TI - MPTP selectively induces haem oxygenase-1 expression in striatal astrocytes. PG - 1573-83 AB - Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta with accompanying evidence of increased oxidative damage, deficits in mitochondrial function and iron deposition. Recently, haem oxygenase-1 levels were reported to be elevated in PD brains. Because this enzyme is involved in the response to oxidative stress and is critical for cellular haem and iron homeostasis, it could play a role in the pathogenesis of PD. Therefore, we investigated the expression of haem oxygenase isoform 1 (HO-1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP triggered a relatively rapid and persistent increase in HO-1 mRNA exclusively in the mouse striatum. In situ hybridization and immunohistochemistry showed HO-1 to be localized to striatal astrocytes. The induction of HO-1 by MPTP was blocked by selegiline and GBR-12909, indicating the protoxin had to be metabolized by monoamine oxidase B and taken up by dopaminergic neurons to exert its action in astrocytes. MPTP did not alter the expression of other enzymes of haem synthesis or degradation nor were the levels of mRNA for haem or iron-binding proteins changed. Thus, expression of HO-1 was not part of a cellular program involving haem biosynthesis or homeostasis. In addition, heat shock proteins were not induced by MPTP. Thus, MPTP elicited a selective transcriptional response in striatal astrocytes. This response appears to be mediated by molecules released from affected dopaminergic nerve terminals in the striatum acting upon neighbouring astrocytes. This signalling pathway and its potential relevance to PD are discussed. FAU - Fernandez-Gonzalez, A AU - Fernandez-Gonzalez A AD - Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale St., Memphis, TN 38105-2794, USA. FAU - Perez-Otano, I AU - Perez-Otano I FAU - Morgan, J I AU - Morgan JI LA - eng GR - P30CA21765/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Carrier Proteins) RN - 0 (Heme-Binding Proteins) RN - 0 (Hemeproteins) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) RN - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.14.14.18 (Hmox1 protein, mouse) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*pharmacology MH - Animals MH - Astrocytes/drug effects/*enzymology MH - Brain/drug effects/*metabolism MH - Brain Stem/enzymology MH - Carrier Proteins/genetics MH - Corpus Striatum/*enzymology MH - Enzyme Induction/drug effects MH - Female MH - Gene Expression Regulation, Enzymologic/*drug effects MH - Heme Oxygenase (Decyclizing)/biosynthesis/*genetics MH - Heme Oxygenase-1 MH - Heme-Binding Proteins MH - Hemeproteins/genetics MH - Kidney/drug effects/metabolism MH - Kinetics MH - Lung/drug effects/metabolism MH - Membrane Proteins MH - Mice MH - Mice, Inbred C57BL MH - RNA, Messenger/genetics MH - Time Factors MH - Transcription, Genetic/drug effects MH - Tyrosine 3-Monooxygenase/metabolism EDAT- 2000/05/03 09:00 MHDA- 2000/08/01 11:00 CRDT- 2000/05/03 09:00 PHST- 2000/05/03 09:00 [pubmed] PHST- 2000/08/01 11:00 [medline] PHST- 2000/05/03 09:00 [entrez] AID - ejn044 [pii] AID - 10.1046/j.1460-9568.2000.00044.x [doi] PST - ppublish SO - Eur J Neurosci. 2000 May;12(5):1573-83. doi: 10.1046/j.1460-9568.2000.00044.x.