Linked Life Data

16153637

Source:http://linkedlifedata.com/resource/pubmed/id/16153637

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2005-9-27
pubmed:abstractText
Serum albumin protects against cell death elicited by various cytotoxic agents; however, conflicting views on the protective mechanism still remain. Hence, we have studied the ability of serum albumin to prevent apoptosis of human neuroblastoma SH-SY 5 Y cells elicited by four compounds known to release Ca(2+) from the endoplasmic reticulum, i.e. dotarizine, flunarizine, thapsigargin and cyclopiazonic acid. Spontaneous basal apoptosis, after 24 h incubation in Dulbecco's Modified Eagle Medium (DMEM) containing 10% serum, was 5%. Dotarizine (30--50 microM) enhanced basal apoptosis to 18--43%, flunarizine (30--50 microM) to 15%, thapsigargin (1--10 microM) to 21--35%, and cyclopiazonic acid (100 microM) to 10%. Serum deprivation augmented basal apoptosis to 20%. Under serum-free medium, 30 microM dotarizine or flunarizine drastically enhanced apoptosis to 63% and 68%, respectively; the increase was milder with 1 microM thapsigargin (37%) and 30 microM cyclopiazonic acid (27%). In serum-free medium, albumin (29 or 49 mg/ml) fully prevented the apoptotic effects of dotarizine, flunarizine and cyclopiazonic acid. The four compounds increased the cytosolic Ca(2+) concentration ([Ca(2+)](c)) in fluo-4 loaded cells; such increase developed slowly to reach a plateau after several minutes, followed by a slow decline. Albumin did not modify the kinetic parameters of such increase. In the absence of serum, dotarizine, flunarizine, thapsigargin, and cyclopiazonic acid caused mitochondrial depolarization in tetramethylrhodamine ethyl ester (TMRE)-loaded cells; depolarization was inhibited by cytoprotective concentrations of albumin. These results suggest that albumin protects cells from entering into apoptosis by preventing mitochondrial depolarization. They also suggest that inhibition of mitochondrial depolarization might become a target to develop new anti-apoptotic compounds with therapeutic neuroprotective potential in stroke, Alzheimer's disease, and other neurodegenerative diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
520
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-11
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16153637-Apoptosis, pubmed-meshheading:16153637-Benzhydryl Compounds, pubmed-meshheading:16153637-Calcium, pubmed-meshheading:16153637-Calcium Channel Blockers, pubmed-meshheading:16153637-Cell Line, Tumor, pubmed-meshheading:16153637-Culture Media, Serum-Free, pubmed-meshheading:16153637-Dose-Response Relationship, Drug, pubmed-meshheading:16153637-Endoplasmic Reticulum, pubmed-meshheading:16153637-Enzyme Inhibitors, pubmed-meshheading:16153637-Flunarizine, pubmed-meshheading:16153637-Humans, pubmed-meshheading:16153637-Membrane Potentials, pubmed-meshheading:16153637-Mitochondria, pubmed-meshheading:16153637-Neuroblastoma, pubmed-meshheading:16153637-Piperazines, pubmed-meshheading:16153637-Serum Albumin, Bovine, pubmed-meshheading:16153637-Thapsigargin, pubmed-meshheading:16153637-Time Factors
pubmed:year
2005
pubmed:articleTitle
Albumin prevents mitochondrial depolarization and apoptosis elicited by endoplasmic reticulum calcium depletion of neuroblastoma cells.
pubmed:affiliation
Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain. soniamaria.gallego@uam.es
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't