Linked Life Data

14527821

Source:http://linkedlifedata.com/resource/pubmed/id/14527821

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-10-6
pubmed:abstractText
Several studies have shown that simvastatin induces apoptosis in a variety of cell lines including vascular smooth muscle cells (VSMCs), but the exactly mechanisms involved in it is not very clear. The aim of this study was to investigate the mechanisms and signal pathways involved in apoptosis induced by simvastatin. When exposed to 30 microM simvastatin, [Ca2+]i in VSMCs increased with time and reached to 336 +/- 52 nM at 6 h, more than four-fold of control (P<0.01, n=5). Verapamil (80 microM), a membrane voltage-dependent Ca2+ channel blocker, attenuated simvastatin-induced augmentation of free calcium concentration from 336 +/- 52 nM to 144 +/- 34 nM (P<0.01). After being exposed to 30 microM simvastatin for 8 h, calpain activity markedly increased (P<0.05, n=4) and reached to more than three-fold of control at 12 h (P<0.01). Caspase-3 was also activated by simvastatin after 12 h. Verapamil and PD150606, a cell-permeable selective calpain inhibitor, significantly inhibited simvastatin-induced augmentation of calpain activity and blocked caspase-3 activation, respectively. Furthermore, 80 microM verapamil and 100 microM PD150606 decreased simvastatin-induced apoptosis rate from 24.2 +/- 1.7% to 7.9 +/- 0.6% (P<0.01, n=4) and 9.5 +/- 1.9% (P<0.01), respectively and also prevented simvastatin-induced DNA laddering. In conclusion, we indicated that simvastatin increases cytosolic free calcium concentration mainly through calcium influx from extracellular solution and then induces apoptosis by activating caspase-3 via calcium-dependent protease calpain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1043-6618
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
571-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Apoptosis induced by simvastatin in rat vascular smooth muscle cell through Ca2+-calpain and caspase-3 dependent pathway.
pubmed:affiliation
Department of Cardiology, The Second Affiliated Hospital, Zhejiang University College of Medicine, Jiefang Road 88#, Hangzhou, Zhejiang 310009, China. chenggang_9@hotmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't