Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heme is a crucial component of many pharmacological and toxicological processes, and studies have suggested that heme deficiency may play a role in cellular ageing. A model of ageing neurons was established using prolonged cultures of BALB/c mouse primary cortical neurons. Aged neurons displayed a senescent phenotype and a marked up-regulation of cathepsin-L expression. Down-regulation of the candidate neuron-specific genes for N-methyl-D-aspartate (NMDA) receptor subunits (NMDAzeta1 and -epsilon2) and neurofilament light peptide (NF-L) were found to be characteristic of the aging process as reported in vivo (Brain Res 907:71-83, 2001; Brain Res Mol Brain Res 99:40-45, 2002). In contrast, the genes for the controlling enzymes of heme synthesis and degradation (5-aminolevulinate synthase 1 and heme oxygenase 1, respectively) were up-regulated, implying depletion of a regulatory heme pool. Inhibition of heme synthesis (by 70-80%) at different enzymic steps by succinyl acetone and N-methylprotoporphyrin IX resulted in the earlier lowered expression of NMDAzeta1 and -epsilon2 and NF-L. Exogenous hemin added to heme-depleted cells rescued the expression of these neuron-specific genes. Culture of cortical neurons from BALB/c Fech(m1Pas) mutant mice demonstrating depressed heme synthesis showed premature senescence and reduced expression of NMDAzeta1 and -epsilon2 receptor subunits and NF-L compared with wild-type cells. Our findings suggest that reduced availability of heme in neurons associated with senescence may have significant effects on synaptic function.
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PMID:Heme deficiency is associated with senescence and causes suppression of N-methyl-D-aspartate receptor subunits expression in primary cortical neurons. 1630 32

The 238th National Meeting and Exposition of the American Chemical Society, held in Washington DC, included topics covering new compounds and developments in the field of medicinal chemistry. This conference report highlights selected presentations on inhibitors of PARP, a heme oxygenase 1 (HO-1) inhibitor, NS3 protease inhibitors, a corticotrophin-releasing factor 1 (CRF-1) receptor antagonist, a cannabinoid receptor antagonist, diacylglycerol acyltransferase inhibitors, cathepsin and chymase receptor inhibitors, and MAPK inhibitors. Investigational drugs discussed include veliparib (Abbott Laboratories), MK-4827 (Merck & Co Inc), OB-24 (Osta Biotechnologies), BMS-339, BMS-764459, BMS-812204 and BMS-640994 (all Bristol-Myers Squibb Co), and JNJ-10311795 (Johnson & Johnson).
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PMID:American Chemical Society--238th National Meeting & Exposition. Developments in medicinal chemistry: part 2. 16-20 August 2009, Washington DC, USA. 1979 5