کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2893367 1172412 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Upregulation of PTEN by CKD712, a synthetic tetrahydroisoquinoline alkaloid, selectively inhibits lipopolysaccharide-induced VCAM-1 but not ICAM-1 expression in human endothelial cells
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Upregulation of PTEN by CKD712, a synthetic tetrahydroisoquinoline alkaloid, selectively inhibits lipopolysaccharide-induced VCAM-1 but not ICAM-1 expression in human endothelial cells
چکیده انگلیسی

AimsWe examined our hypothesis that CKD712, (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, selectively inhibits vascular adhesion molecule-1 (VCAM-1) but not intracellular adhesion molecule-1 (ICAM-1) expression via activation of PTEN in human umbilical vein endothelial cells (HUVECs) activated with lipopolysaccharide (LPS).Methods and resultsIn order to do this, cells were pretreated with CKD712 1 h prior to stimulate with LPS (1 μg/ml) for 16 h, and VCAM-1 and ICAM-1 levels were measured by Western blot. We found that CKD712 dose-dependently inhibited VCAM-1 but not ICAM-1 expression after LPS stimulation in HUVECs. Furthermore CKD712 blocked the attachment of monocytes (U397) to HUVECs by LPS. Differential effect of CKD712 on adhesion molecules was mediated via regulation of PI3K/Akt signaling. It was found that CKD712 is able to significantly upregulate PTEN activity through its dephosphorylation. The inhibitory effect of CKD712 in activated HUVECs was reversed by siPTEN. In addition, administration of CKD712 (10 mg/kg) inhibited VCAM-1 but not ICAM-1 expression in thoracic aorta of LPS (10 mg/kg)-treated rats.ConclusionOur results indicate that upregulation of PTEN by CKD712 selectively inhibit VCAM-1 expression in LPS-treated HUVECs. Thus CKD712 may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 207, Issue 2, December 2009, Pages 412–419
نویسندگان
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