Linked Life Data

20938651

Source:http://linkedlifedata.com/resource/pubmed/id/20938651

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2010-11-24
pubmed:abstractText
The cluster of neurodegenerative disorders in the western Pacific termed amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) has been repeatedly linked to the use of seeds of various species of cycad. Identification and chemical synthesis of the most toxic compounds in the washed cycad seeds, a variant phytosteryl glucosides, and even more toxic cholesterol ?-D-glucoside (CG), which is produced by the human parasite Helicobacter pylori, provide a possibility to study in vitro the mechanisms of toxicity of these compounds. We studied in detail the effects of CG on the respiratory activities and generation of reactive oxygen species (ROS) by nonsynaptic brain and heart mitochondria oxidizing various substrates. The stimulatory effects of CG on respiration and ROS generation showed strong substrate dependence, suggesting involvement of succinate dehydrogenase (complex II). Maximal effects on ROS production were observed with 1 ?mol CG/1 mg mitochondria. At this concentration the cycad toxins ?-sitosterol-?-D-glucoside and stigmasterol-?-D-glucoside had effects on respiration and ROS production similar to CG. However, poor solubility precluded full concentration analysis of these toxins. Cholesterol, stigmasterol and ?-sitosterol had no effect on mitochondrial functions studied at concentrations up to 100 ?mol/mg protein. Our results suggest that CG may influence mitochondrial functions through changes in the packing of the bulk membrane lipids, as was shown earlier by Deliconstantinos et al. (Biochem Cell Biol 67:16-24, 1989). The neurotoxic effects of phytosteryl glucosides and CG may be associated with increased oxidative damage of neurons. Unlike heart mitochondria, in activated neurons mitochondria specifically increase ROS production associated with succinate oxidation (Panov et al., J Biol Chem 284:14448-14456, 2009).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1432-1424
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
237
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
71-7
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
In vitro effects of cholesterol ?-D-glucoside, cholesterol and cycad phytosterol glucosides on respiration and reactive oxygen species generation in brain mitochondria.
pubmed:affiliation
Carolinas Neuromuscular/ALS Research Laboratory, Cannon Research Center, Carolinas Medical Center, 1000 Blythe Blvd, Charlotte, NC 28203, USA. alexander.panov55@gmail.com
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural