Linked Life Data

17274957

Source:http://linkedlifedata.com/resource/pubmed/id/17274957

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-4-9
pubmed:abstractText
TRPV1 is a non-selective cationic channel that is activated by capsaicin, acidic pH and thermal stimuli. Sustained TRPV1 channel activation causes severe cytotoxicity that leads to cell death. In this study, we investigated the mechanisms of capsaicin-induced cytotoxicity in HEK293 cells stably expressing TRPV1 with a focus on protein synthesis regulation and cytoskeleton reorganization. Capsaicin inhibited protein synthesis in TRPV1-expressing HEK cells with an IC(50) of 15.6nM and depolymerized microtubules within 10min after exposure. These effects were completely blocked by pretreatment of cells with the TRPV1 antagonist A-425619, both in the presence and absence of extracellular calcium. Protein synthesis inhibition induced by capsaicin was not a result of eIF2alpha hyperphosphorylation, but rather closely correlated with cytosolic calcium elevation caused by calcium flux through cell surface and intracellular TRPV1, and/or ER calcium depletion through intracellular TRPV1. Microtubule dependent cell process shrinkage may serve as a mechanism for rapid alteration of the neurotransmission network upon TRPV1 activation. Taken together, the present studies demonstrate that intracellular pool of TRPV1 plays an important role in regulating cell morphology and viability upon receptor activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1635-45
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Capsaicin causes protein synthesis inhibition and microtubule disassembly through TRPV1 activities both on the plasma membrane and intracellular membranes.
pubmed:affiliation
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. ping.han@abbott.com
pubmed:publicationType
Journal Article