Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten-day administration of the glutamate-cysteine ligase inhibitor L-buthionine-[S,R]-sulfoximine (BSO; 20 or 30 mM in drinking water) to adult male Sprague-Dawley rats induced 50-60% glutathione depletion (p<0.001) and elevated aortic ring reactive oxygen species release and tissue and plasma H2O2 concentrations (p<0.001) compared to control animals (CON) that consumed normal drinking water. In contrast to previous studies using tail cuff plethysmography methods, BSO had no significant effect on systolic blood pressure assessed by indwelling femoral artery catheters in conscious animals (10-day values, 119+/-3 mn Hg vs 122+/-4 mm Hg in CON vs BSO, respectively). Thoracic aorta rings were excised for in vitro assessment of vasomotor function. BSO shifted the phenylephrine (PE) dose-response curve to the left (p=0.003), lowering the EC50 for PE contraction (from -6.752+/-0.056 to -7.056+/-0.055 log units; p=0.001). Endothelium-dependent relaxation to acetylcholine (ACh) was significantly blunted (p=0.019) and the EC50 for ACh relaxation was significantly increased (from -7.428+/-0.117 to -7.129+/-0.048 log units; p=0.02) in BSO vs CON. Endothelium-independent vasorelaxation to sodium nitroprusside was similar in BSO and CON groups. Thoracic aorta immunoblot analyses revealed increases in endothelial nitric oxide synthase, superoxide dismutase 1 and 2, and soluble guanylate cyclase in BSO vs CON (all p<0.01). Thus, enhanced PE contraction, blunted endothelium-dependent relaxation, and adaptations in nitric oxide bioavailability pathways provide the first evidence of chronic, in vivo BSO-induced, oxidative stress-mediated direct effects on the vasomotor function of arteries.
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PMID:Glutathione depletion in vivo enhances contraction and attenuates endothelium-dependent relaxation of isolated rat aorta. 1645 98

Different somatic motor neuron subpopulations show a differential vulnerability to degeneration in diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy and spinobulbar muscular atrophy. Studies in mutant superoxide dismutase 1 over-expressing amyotrophic lateral sclerosis model mice indicate that initiation of disease is intrinsic to motor neurons, while progression is promoted by astrocytes and microglia. Therefore, analysis of the normal transcriptional profile of motor neurons displaying differential vulnerability to degeneration in motor neuron disease could give important clues to the mechanisms of relative vulnerability. Global gene expression profiling of motor neurons isolated by laser capture microdissection from three anatomical nuclei of the normal rat, oculomotor/trochlear (cranial nerve 3/4), hypoglossal (cranial nerve 12) and lateral motor column of the cervical spinal cord, displaying differential vulnerability to degeneration in motor neuron disorders, identified enriched transcripts for each neuronal subpopulation. There were striking differences in the regulation of genes involved in endoplasmatic reticulum and mitochondrial function, ubiquitination, apoptosis regulation, nitrogen metabolism, calcium regulation, transport, growth and RNA processing; cellular pathways that have been implicated in motor neuron diseases. Confirmation of genes of immediate biological interest identified differential localization of insulin-like growth factor II, guanine deaminase, peripherin, early growth response 1, soluble guanylate cyclase 1A3 and placental growth factor protein. Furthermore, the cranial nerve 3/4-restricted genes insulin-like growth factor II and guanine deaminase protected spinal motor neurons from glutamate-induced toxicity (P < 0.001, ANOVA), indicating that our approach can identify factors that protect or make neurons more susceptible to degeneration.
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PMID:Global gene expression profiling of somatic motor neuron populations with different vulnerability identify molecules and pathways of degeneration and protection. 2082 31