Abstract:
:This study aimed to elucidate whether the effect of cilostazol to suppress apoptotic cell death is directly coupled to cAMP-dependent protein kinase activation in human umbilical vein endothelial cells (HUVECs). After exposure of HUVECs to LPS (1 microgml(-1)) for 18 h, the endothelial cells irregularly aggregated with loss of cobblestone appearance, which was reversed by cilostazol (1-100 microM), as well as by cilostamide (cilostazol analog), and cilostazol metabolites (OPC-13015 and OPC-31213), respectively. LPS-stimulated production of reactive oxygen species (ROS) was significantly reduced by cilostazol (0.1-10 microM). In line with these, LPS (1 microgml(-1))- and TNF-alpha (200 ngml(-1))-induced DNA fragmentation, assessed by agarose gel electrophoresis, was significantly reduced by treatment with cilostazol (10 microM) as well as by dibutyryl cAMP (100 microM). This effect was reversed by cAMP-dependent protein kinase inhibitor, Rp-cAMPs (200 microM). Further, LPS (1 microgml(-1))-induced decrease in Bcl-2 and increase in Bax protein expression were fully reversed by cilostazol (10 microM) and dibutyryl cAMP (100 microM), all of which were antagonized by Rp-cAMPs (200 microM). Taken together, cilostazol effectively protected HUVECs from LPS- and TNF-alpha-induced cell death associated with oligonucleosomal DNA fragmentation via activation of cAMP-dependent protein kinase.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Kim MJ,Lee JH,Park SY,Hong KW,Kim CD,Kim KY,Lee WSdoi
10.1016/j.phrs.2006.05.006subject
Has Abstractpub_date
2006-10-01 00:00:00pages
261-7issue
4eissn
1043-6618issn
1096-1186pii
S1043-6618(06)00106-Xjournal_volume
54pub_type
杂志文章abstract::The blood-brain barrier (BBB) keeps the central nervous system (CNS) safe from various brain diseases, while the BBB makes it difficult for effective drugs to enter the CNS. Mfsd2a is specifically expressed on the cell membrane of brain-microvascular endothelial cell (BMEC) and is implicated in the delivery of some su...
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更新日期:2012-03-01 00:00:00
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更新日期:2016-09-01 00:00:00
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更新日期:1999-10-01 00:00:00
abstract:BACKGROUND:Many flavonoids have various beneficial actions like anti-inflammatory, anti-carcinogenic properties and many other clinical conditions. Astilbin is one such flavanoid compound having many physiological as well as pharmacological actions. PURPOSE:To summarize the important findings from the research conduct...
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