Effect of vascular endothelial growth factor and epidermal growth factor on iatrogenic apoptosis in human endothelial cells.

Abstract:

:To study the effect of growth factors on iatrogenic apoptosis, we examined the influence of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) on staurosporine-induced apoptosis in primary cultures of human umbilical vein endothelial cells (HUVEC). Apoptosis was evaluated by a cell viability test, the TUNEL-POD assay and the activation of the pro-apoptotic caspase-3. Staurosporine (10-100nM) caused the activation of caspase-3. This effect was manifest after 2hr of incubation and reached its maximum after 5hr. Severe loss of viability followed within 18hr. VEGF or EGF (10-100ng/mL) added together with staurosporine decreased the activation of caspase-3. The loss of viability was 24hr delayed. The action of growth factors was observed at 1% serum concentration but also at concentration optimal for HUVEC survival (10%, v/v). Furthermore, the inhibition of PI-3 kinase (PI-3K) by wortmannin or LY294002 as well as the inhibition of MEK by PD098059 or U0126 prevented the protective effect of VEGF and EGF. Western blotting analysis showed that after 3hr of incubation with staurosporine the level of the anti-apoptotic protein Mcl-1 decreased and this effect was reverted by VEGF. It is concluded that VEGF and EGF antagonize the pro-apoptotic action of staurosporine by the combined signalling of PI-3K and ERKs pathways.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Vinci MC,Visentin B,Cusinato F,Nardelli GB,Trevisi L,Luciani S

doi

10.1016/j.bcp.2003.09.007

subject

Has Abstract

pub_date

2004-01-15 00:00:00

pages

277-84

issue

2

eissn

0006-2952

issn

1873-2968

pii

S0006295203007366

journal_volume

67

pub_type

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