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)

A marked decrease in the activity of mitochondrial complex II (succinate dehydrogenase, SD) has been found in the brains of Huntington's disease (HD) patients. Here we have examined the possibility that SD inhibitors might produce their toxic action by increasing corticostriatal glutamatergic transmission. We report that SD inhibitors produce a durable augmentation of NMDA-mediated corticostriatal excitation (DANCE) in striatal spiny neurons, but not in striatal cholinergic interneurons. DANCE involves increased intracellular calcium, activation of MAP kinase ERK and is critically dependent upon endogenous dopamine (DA) acting via D2-like receptors. This pathological form of corticostriatal synaptic plasticity might play a key role in the regional and cell-type specific neuronal death observed in HD.
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PMID:An abnormal striatal synaptic plasticity may account for the selective neuronal vulnerability in Huntington's disease. 1148 2

Brain-derived neurotrophic factor (BDNF) governs both the selective survival of neurons during development and the experience-based regulation of synaptic strength throughout life. BDNF produced a concentration-dependent increase in the respiratory control index (RCI, a measure of the efficiency of respiratory coupling, ATP synthesis and organelle integrity) of rat brain mitochondria. This effect was mediated via a MAP kinase pathway and highly specific for oxidation of glutamate plus malate (complex I) by brain mitochondria. The oxidation by brain mitochondria of the complex II substrate succinate was unaffected by BDNF. The failure of BDNF to modify respiratory activity associated with mitochondrial preparations isolated from rat liver indicates that the actions of the neurotrophin are tissue specific. BDNF also increased the RCI values associated with Ca2+ -induced respiration to a similar extent. This is the first demonstration that BDNF, in addition to modifying neuronal plasticity, can modify brain metabolism and the efficiency of oxygen utilization. The finding that neurotrophins can alter mitochondrial oxidative efficiency has important implications for neurodegenerative and psychiatric diseases.
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PMID:BDNF increases rat brain mitochondrial respiratory coupling at complex I, but not complex II. 1534 90

Paragangliomas (PGLs) have widely different metastastic potentials. Two different types of PGLs can be defined by expression profiling. Cluster 1 PGLs exhibit VHL and/or succinate dehydrogenase (SDH) mutations and a pseudohypoxic phenotype. RET and neurofibromatosis type 1 (NF1) mutations occur in cluster 2 tumors characterized by deregulation of the RAS/RAF/MAP kinase signaling cascade. Sporadic PGLs can exhibit either profile. During sustained hypoxia, a natural antisense transcript of hypoxia-inducible factor 1 (aHIF) is expressed. The role of aHIF in the metastatic potential of PGL has not yet been investigated. The aim was to test the hypothesis that genotype-specific overexpression of aHIF is associated with an increased metastatic potential. Tumor samples were collected from 87 patients with PGL. Quantitative PCR was performed for aHIF, vascular endothelial growth factor (VEGF), aquaporin 3, cytochrome b561, p57Kip2, slit homolog 3, and SDHC. Expression was related to mutation status, benign versus malignant tumors, and metastasis-free survival. We found that both aHIF and VEGF were overexpressed in cluster 1 PGLs and in metastatic tumors. In contrast, slit homolog 3, p57Kip2, cytochrome b561, and SDHC showed overexpression in non-metastatic tumors, whereas no such difference was observed for aquaporin 3. Patients with higher expression levels of aHIF and VEGF had a significantly decreased metastasis-free survival. Higher expression levels of SDHC are correlated with an increased metastasis-free survival. In conclusion, we not only demonstrate a higher expression of VEGF in cluster 1 PGL, fitting a profile of pseudohypoxia and angiogenesis, but also of aHIF. Moreover, overexpression of aHIF and VEGF marks a higher metastatic potential in PGL.
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PMID:Overexpression of the natural antisense hypoxia-inducible factor-1alpha transcript is associated with malignant pheochromocytoma/paraganglioma. 2158 46