In:
Journal of Cell Science, The Company of Biologists, Vol. 108, No. 7 ( 1995-07-01), p. 2629-2644
Abstract:
Previous work demonstrated that 12(S)-HETE [12(S)hydroxyeicosatetraenic acid], a lipoxygenase metabolite of arachidonic acid, stimulates the surface expression of integrin αvβ3 on mouse lung vascular endothelial cells (CD clone 3) in a post-transcriptional and protein kinase C (PKC)-dependent fashion. In this study we examined the effect of 12(S)-HETE on the expression of integrin receptors αvβ3 and α5β1 in a different clone of a mouse endothelial cell population derived from lung microvasculature (designated CD clone 4). The results indicated that 12(S)-HETE transcriptionally activates the gene expression of integrin αv as assessed by quantitative reverse transcription/polymerase chain reaction/Southern hybridization, RNase protection assay, solution hybridization, and northern blotting. The induction of αv mRNA occurred within 1 hour, peaked at ∼4 hours (2-to 4-fold increase), persisted for up to 16 hours, and thereafter gradually declined. The PKC activator phorbol 12-myristate 13-acetate (PMA) induced the αv mRNA, in a similar way. 12(S)-HETE treatment did not, in contrast, alter the mRNA levels of integrin subunit α5 or β1. The induction of αv mRNA appeared to be protein synthesis-independent, since cycloheximide did not alter the 12(S)-HETE effect. 12(S)-HETE also did not appear to alter the mRNA halflife of αv. On the other hand, 12(S)-HETE-induced increase in αv mRNA levels was PKC-dependent, since pretreatment of CD clone 4 cells with calphostin C significantly inhibited 12(S)-HETE-increased αv mRNA. Nuclear runoff experiments revealed that the increase in αv mRNA results from an enhanced gene transcription. Facilitated αv gene transcription resulted in an increased surface expression of αvβ3 protein, which resulted in an increased cell adhesion to vitronectin. The above observations, in conjunction with our previous experimental data, suggest that 12(S)-HETE may employ diverse mechanisms to stimulate the integrin αvβ3 expression in vascular endothelial cells, which could play important roles in tumor cell adhesion, angiogenesis, hemostasis, and many other vascular events.
Type of Medium:
Online Resource
ISSN:
0021-9533
,
1477-9137
DOI:
10.1242/jcs.108.7.2629
Language:
English
Publisher:
The Company of Biologists
Publication Date:
1995
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
