Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the regulatory effects of neural activation and trophic factors on the selective accumulation of succinate dehydrogenase (SDH; EC 1.3.99.1) activity at the endplate, as well as within subsarcolemmal and intermyofibrillar regions of rat soleus muscle fibers. The role of activation was assessed by stimulation of tetrodotoxin (TTX)-inactivated nerves distal to the site of drug application. We also studied whether ciliary neurotrophic factor (CNTF) is involved in regulating the postsynaptic accumulation of SDH. Using quantitative microphotometry, we found that daily stimulation of quiescent but intact nerves prevented the TTX-induced decrease in SDH activity within extrajunctional regions, whereas, at the endplate, the counteraction was partial (30%). Thus it appears that endplate levels of this enzyme are regulated by a complex mechanism involving an interaction between neuromuscular activation and trophic factors. We also found that daily CNTF administration counteracted the denervation-associated loss of SDH activity exclusively within the intermyofibrillar compartment, suggesting that CNTF treatment mimics the effects of activity on SDH levels within the core region of denervated fibers, but under these conditions does not influence the endplate accumulation of this enzyme.
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PMID:Regulation of succinate dehydrogenase within muscle fiber compartments by nerve-mediated activity and CNTF. 876 87

In response to injury and degeneration, astrocytes hypertrophy, extend processes, and increase production of glial fibrillary acidic protein (GFAP), an intermediate filament protein located within their cytoplasm. The present study tested the hypothesis that GFAP expression alters the vulnerability of neurons to excitotoxic and metabolic insult induced by 3-nitroproprionic acid (3-NP), an irreversible inhibitor of mitochondrial complex II activity or the excitotoxin quinolinic acid (QA). In this respect, adult GFAP knockout mice (KO) and wild-type control mice (WT) received unilateral intrastriatal injections of 3-NP (200 nmol/microl) or QA (100 nmol/microl) and were killed 1, 2, or 4 weeks later. Lesion volume and neuronal counts were quantified using unbiased stereologic principles. For both QA and 3-NP lesions, a significant decrease in lesion volume and an increase in striatal projection neurons were seen in GFAP KO mice compared with WT mice. Enzyme-linked immunoassay analysis revealed increased basal levels of glial cell derived neurotrophic factor (GDNF) relative to WT mice. In contrast, no differences were observed in the expression of ciliary neurotrophic factor or nerve growth factor. These data strongly suggest that the expression of GFAP is implicated with the production of GDNF to a degree that confers neuroprotection after an excitotoxic or metabolic insult.
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PMID:GFAP knockout mice have increased levels of GDNF that protect striatal neurons from metabolic and excitotoxic insults. 1274 70

In a previous study, the ciliary neurotrophic factor (CNTF) were demonstrated to lead to weight-loss partly by up-regulating the energy metabolism and the expression of uncoupling protein-1, mitochondrial transcription factor A and nuclear respiratory factor-1 in adipose tissues or muscle. To investigate the up-stream regulators of the expression, recombinant human CNTF (rhCNTF) (0.1, 0.3 and 0.9 mg/kg/day subcutaneously) were administered to KK-Ay mice for 30 days, resulting in reduction of perirenal fat mass, serum free fatty acids and islet triacylglycerol; furthermore, the values of oral glucose tolerance test were found improved. In brown adipose tissues, the gene expressions of peroxisome proliferator-activated receptor alpha (PPARalpha) and peroxisome proliferator-activated receptor coactivator-1 alpha (PGC-1alpha) were found to be up-regulated by rhCNTF. To the best of our knowledge, the changes of gene expression of PPARalpha and PGC-1alpha represent new insights into the mechanisms of anti-diabetes by rhCNTF. In addition, the activity of mitochondrial complexII was found to be increased by rhCNTF. Stimulation of PPARalpha, PGC-1alpha, uncoupling protein-1 and enhanced activity of mitochondrial complex II may be associated with the effects of anti-diabetes. The present study indicates new mechanisms of the activity and mechanisms on anti-diabetes of rhCNTF, which may be a novel anti-diabetes reagent partly acting by enhancing energy metabolism.
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PMID:The novel mechanism of recombinant human ciliary neurotrophic factor on the anti-diabetes activity. 1765 6