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Evidence for conversion of N-Tyr-MIF-1 into MIF-1 by a specific brain aminopeptidase.
MedLine Citation:
PMID:  20488055     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
N-Tyr-MIF-1 (Tyr-Pro-Leu-Gly.NH(2)), an immunoreactive neuropeptide exhibiting saturable high affinity binding in rat brain was found to be converted into MIF-1 (Pro-Leu-Gly.NH(2)) by a specific brain aminopeptidase present in rat brain homogenates or cytosol, but with low activity associated with synaptosomal plasma membranes and microsomes. Conversion occurred at a rate of 16 ?mol per g w/wt per h and was unaffected by puromycin but inhibited by bestatin (I(50), 5 x 10(?5) M). Aminopeptidases purified from cytosolic fractions of rat brain (arylamidase), mouse brain (Mn(2+)-activated aminopeptidase) or porcine kidney (leucine aminopeptidase) were inactive towards N-Tyr-MIF-1 but degraded MIF-1 with release of Leu-Gly.NH(2) as detected by RP-HPLC procedures. Morphiceptin (Tyr-Pro-Phe-Pro.NH(2)), a ? opioid agonist, also acted as a substrate for the N-Tyr-MIF-1 converting enzyme with cleavage of the Tyr-Pro bond. These tetrapeptides, but not MIF-1 or its N-blocked analogs, were degraded in vitro by a metalloendopeptidase purified from kidney membranes. Since dipeptide products were not detected for crude extracts, a significant role for brain metalloendopeptidase on turnover can be excluded. Thus the results point to the presence of a specific (X-Pro-degrading) aminopeptidase in brain cytosol as an enzyme responsible for converting N-Tyr-MIF-1 and inactivating morphiceptin.
Authors:
N Marks; M J Berg; A J Kastin; D H Coy
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neurochemistry international     Volume:  6     ISSN:  0197-0186     ISO Abbreviation:  Neurochem. Int.     Publication Date:  1984  
Date Detail:
Created Date:  2010-05-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  347-53     Citation Subset:  -    
Affiliation:
Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, Ward's Island, NY 10035, U.S.A.
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