Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is recognized that monoamine reuptake inhibitors (MARIs) exert beneficial effects in the treatment of major depression and general anxiety disorder. The aim of this study was to identify proteins regulated by this class of antidepressant using a proteome differential profiling approach. Either venlafaxine or fluoxetine was administered systemically to adult rats for 2 weeks, and protein patterns from rat hippocampal cytosolic extracts were compared by two-dimensional gel electrophoresis. Silver-stained protein spots displaying differential expression were identified by mass spectrometry. Thirty-three protein spots were modulated by both drug treatments compared to controls. The classification of several proteins that were sorted by function suggested convergent pathway activities for both MARIs at the post-receptor level. These included proteins associated with neurogenesis (insulin like growth factor 1 (IGF-1), glia maturation factor [GMF]-beta), outgrowth/maintenance of neuronal processes (hippocampal cholinergic neurostimulating peptide [HCNP], PCTAIRE-3), and with neural regeneration/axonal guidance collapsin response mediator protein (CRMP-2) systems. Other modulated proteins indicated an increase in neuronal vesicular cell trafficking and synaptic plasticity (Ras-related protein 4a (Rab4a), Ras-related protein 1b (Rab1b), heat shock protein 10 [HSP10]), as well as neurosteroidogenic (hydroxysteroid sulfotransferase A) and possible anti-apoptotic (dimethylargininase-1 L-N,N-dimethylarginine dimethylaminohydrolase-1 [DDAH-1], pyruvate dehydrogenase-E1 [PDH-E1], antioxidant protein-2 [AOP-2]) pathway-mediated regulatory events. Parallel studies to investigate further the effects of venlafaxine and fluoxetine on adult hippocampal neurogenesis in vivo by quantitative bromodeoxyuridine immunolabeling revealed a significant drug-induced increase in the proliferation rate and long-term survivability of progenitor stem cells located in the subgranular zone. These data suggest that MARIs share wide-ranging proteome changes within the hippocampal formation, beyond 5-HT/NE neurotransmission. This may reflect long-term functional adaptations required for antidepressant activity.
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PMID:Proteomic analysis of protein changes developing in rat hippocampus after chronic antidepressant treatment: Implications for depressive disorders and future therapies. 1474 28

In large population-based cohorts, elevated plasma levels of asymmetric dimethylarginine (ADMA) were found to be associated with cardiovascular events and mortality. Impairment of nitric oxide (NO) synthesis from l-arginine has been postulated as underlying mechanism. In the present review, we compare different experimental models of NOS deficiency or overexpression with corresponding models of altered metabolism of ADMA by dimethylarginine dimethylaminohydrolase (DDAH). The latter models show a considerable overlap with the pathophysiological features of impaired NO synthesis, such as impaired endothelial function, elevation of blood pressure, and microvascular fibrosis. In line with these findings, first data regarding genetic variation of DDAH-metabolism in humans are reminiscent of the (rather modest) effects previously observed with polymorphisms of the eNOS gene. However, several peculiar observations suggest that ADMA- or DDAH-related pathology may extend beyond impairment of NO-mediated signalling. Notably, the complete knock out of DDAH1 appears to be lethal while triple NOS(-/-) mice are viable. Moreover, some ADMA-mediated pathology appears to respond rather to ACE-inhibition than to l-arginine. Here, a further investigation of alternative target enzymes for ADMA and other endogenous DDAH substrates is warranted.Taken together, the current data suggest that ADMA-related pathology can largely but not completely be explained by impaired NO metabolism.
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PMID:ADMA and the role of the genes: lessons from genetically modified animals and human gene polymorphisms. 1966 22