Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.3.5.1 (
succinate dehydrogenase
)
8,177
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The precise cause of neuronal cell death in Huntington's disease (HD) is not known. Systemic administration of 3-nitropropionic acid (3-NP), an irreversible
succinate dehydrogenase
inhibitor, not only induces a cellular ATP depletions but also causes a selective striatal degeneration similar to that seen in HD. Recent accumulating reports have shown that ginseng saponins (
GTS
), the major active ingredients of Panax ginseng, have protective effects against neurotoxin insults. In the present study, we examined in vitro and in vivo effects of
GTS
on striatal neurotoxicity induced by repeated treatment of 3-NP in rats. Here, we report that systemic administration of
GTS
produced significant protections against systemic 3-NP- and intrastriatal malonate-induced lesions in rat striatum with dose-dependent manner.
GTS
also improved significantly 3-NP-caused behavioral impairment and extended survival. However,
GTS
itself had no effect on 3-NP-induced inhibition of
succinate dehydrogenase
activity. To explain the mechanisms underlying in vivo protective effects of
GTS
against 3-NP-induced striatal degeneration, we examined in vitro effect of
GTS
against 3-NP-caused cytotoxicity using cultured rat striatal neurons. We found that
GTS
inhibited 3-NP-induced intracellular Ca(2+) elevations.
GTS
restored 3-NP-caused mitochondrial transmembrane potential reduction in cultured rat striatal neurons.
GTS
also prevented 3-NP-induced striatal neuronal cell deaths with dose-dependent manner. The EC(50) was 12.6 +/- 0. 7microg/ml. These results suggest that in vivo protective effects of
GTS
against 3-NP-induced rat striatal degeneration might be achieved via in vitro inhibition of 3-NP-induced intracellular Ca(2+) elevations and cytotoxicity of striatal neurons.
...
PMID:Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats. 1581 8
