Document Detail

The regulation of heme turnover and carbon monoxide biosynthesis in cultured primary rat olfactory receptor neurons.
MedLine Citation:
PMID:  8795618     Owner:  NLM     Status:  MEDLINE    
Heme oxygenase (HO) converts heme to carbon monoxide (CO) and biliverdin, which is metabolized rapidly to bilirubin. CO is implicated as an intercellular messenger, whereas bilirubin could function as an antioxidant. These cellular functions differ significantly from those of HO in peripheral tissues, in which it degrades heme from senescent erythrocytes, suggesting that the regulation of HO may differ in neurons from that in other tissues. Among neurons, olfactory receptor neurons have the highest level of HO activity. Metabolic labeling with [2-14C]glycine or delta-[3H]aminolevulinic acid ([3H]ALA) was used to investigate heme metabolic turnover and CO biosynthesis in primary cultures of olfactory receptor neurons. The production rates of heme precursors and metabolites from [14C]glycine over 6 hr were (in pmol/mg protein): 100 for ALA, 8.2 for heme, and 2.9 for CO. Taking into account endogenous heme content, the amount of total CO production was determined to be 1.6 nmol/mg protein per 6 hr. Heme biosynthesis usually is subject to end-product negative feedback at the level of ALA synthase. However, metabolic control in these neurons is different. Both heme concentration (heme formation) and HO activity (heme degradation) were enhanced significantly during immature stage of neuronal differentiation in culture. Neuronal maturation, which is accelerated by transforming growth factor-beta 2 (TGF-beta 2), suppressed the activities of both heme biosynthesis and degradation. To explore the physiological importance of this endogenous production of CO, we examined the potency of CO as a soluble guanylyl cyclase activator. Exogenous CO (10-30 microM), comparable to endogenous CO production, significantly activated guanylyl cyclase, suggesting that HO activity may regulate cGMP levels in the nervous system.
T Ingi; G Chiang; G V Ronnett
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  16     ISSN:  0270-6474     ISO Abbreviation:  J. Neurosci.     Publication Date:  1996 Sep 
Date Detail:
Created Date:  1996-12-11     Completed Date:  1996-12-11     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5621-8     Citation Subset:  IM    
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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MeSH Terms
Carbon Monoxide / metabolism*,  pharmacology
Cell Differentiation
Cells, Cultured
Cyclic GMP / metabolism
Heme / antagonists & inhibitors,  metabolism*,  pharmacology
Heme Oxygenase (Decyclizing) / metabolism
Nerve Tissue / metabolism
Neurons, Afferent / cytology,  metabolism
Olfactory Pathways / cytology,  metabolism*
Sensory Receptor Cells / metabolism*
Reg. No./Substance:
14875-96-8/Heme; 630-08-0/Carbon Monoxide; 7665-99-8/Cyclic GMP; EC Oxygenase (Decyclizing)

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