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)

The inhibitor of mitochondrial enzyme succinate dehydrogenase, 3-nitropropionic acid (3-NPA), induces cellular energy deficit followed by oxidative stress, secondary excitotoxicity and neuronal degeneration. The fast activation of Jun and Fos proteins and other proteins encoding inducible transcription factors (ITFs) occurs in most tissues upon exposure to a variety of stressors including exposure to mitochondrial inhibitors. However, the consequences of this activation can differ dramatically in different organs. For example, while activation of the same ITFs may lead to apoptosis and necrosis in neurons it may stimulate liver regeneration. Here, we report the alterations in mRNAs levels of c-Fos, JunB, and Krox20 proteins induced in the rat brain and liver by the acute exposure to 3-NPA at 30 mg/kg, s.c. While the increase of c-fos transcripts was observed in both the hippocampus and liver, the junb transcript increased in the hippocampus but decreased in the liver. No changes were observed in krox-20 mRNA in the hippocampus. Interestingly, there was a large variation in krox-20 mRNA levels in the liver among animals within the same experimental group. In conclusion, out of the three ITFs transcripts examined here junb may activate different pathways depending on the tissue as indicated by differential responses to mitochondrial inhibition in the hippocampus and liver.
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PMID:The differential JunB responses to inhibition of succinate dehydrogenase in rat hippocampus and liver. 1589 99

Reactive astrocytosis seems to be strongly implicated in the development and maintenance of inflammatory and neurodegenerative disorders. We design a new toxic model treatment with 3-nitropropionic acid (3-NP), a mitochondrial complex II irreversible inhibitor, to induce in rats Huntington's disease (HD) like syndrome, characterized by hindlimb dystonia, involuntary choreiform movements and reduced global activity. In an attempt to find out whether molecular and morphological changes in the neuro-glial network could be involved in the pathogenesis of this disease, we developed a protocol of subchronic intra-peritoneal 3-NP intoxication. Moreover we set up specific, highly discriminative, behavioral tests to detect very early mild motor disabilities in 3-NP treated rats. This treatment did not cause severe cell death. However, in the Caudate-Putamen (CPu) of all 3-NP treated animals we found a massive astrogliosis, revealed by increased GFAP levels, paralleled by changes of the glial glutamate transporter GLAST distribution. To these glial changes we detected a transcriptional upregulation of c-fos and Sub-P in the striatal medium spiny neurons (MSN). We propose that this model of 3-NP intoxication along with the designed set of behavioral analyses allow to unmask in a very early phase the motor deficits and the underlying morpho-molecular changes associated to the onset of motor disabilities in the HD-like syndrome. Therefore this model unveil the key role played by the different components of the tripartite synapse in the pathogenesis of the HD, a putative non-cell-autonomous disease.
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PMID:Discriminative behavioral assessment unveils remarkable reactive astrocytosis and early molecular correlates in basal ganglia of 3-nitropropionic acid subchronic treated rats. 1979 53