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Effect of MG132, a proteasome inhibitor, on the expression of growth related oncogene protein-alpha in human umbilical vein endothelial cells.

Abstract：

:Growth related oncogene protein-alpha (GRO-alpha) is a member of C-X-C chemokine and plays an important role in inflammatory responses. Expression of GRO gene family is regulated by a number of factors at both transcriptional and posttranscriptional levels. In the present study, we have addressed the possible regulation of GRO-alpha expression by ubiquitin-proteasome system. Cultures of human umbilical vein endothelial cells were treated with a proteasome inhibitor, MG132, and the levels of GRO-alpha mRNA were analyzed by reverse transcription-polymerase chain reaction or northern blotting. Levels of GRO-alpha protein in the cell-conditioned medium were determined by enzyme-linked immunosorbent assay. MG132 alone increased the levels of GRO-alpha mRNA and protein; however, it did not affect the GRO-alpha mRNA induced by lipopolysaccharide (LPS) and inhibited the LPS-induced decrease in IkappaB levels. Other proteasome inhibitors, MG115 and lactacystin, also induced the expression of GRO-alpha mRNA. MG132 induced the phosphorylation of p38 MAPK, MEK and JNK. Pretreatment of the cells with SB203580, an inhibitor of p38 MAPK, suppressed the MG132-induced GRO-alpha expression, but pretreatment of the cells with U0126, PD98059 or SP600125, inhibitors of MEK1/2 or JNK, did not influence the effect of MG132. We conclude that MG132 upregulates GRO-alpha expression in vascular endothelial cells, at least in part, through the activation of p38 MAPK.

journal_name

Cytokine

journal_title

Cytokine

authors

Shibata T,Imaizumi T,Matsumiya T,Tamo W,Hatakeyama M,Yoshida H,Munakata H,Fukuda I,Satoh K

doi

10.1016/s1043-4666(03)00271-0

keywords:

subject

Has Abstract

pub_date

2003-11-07 00:00:00

pages

67-73

issue

3

eissn

1043-4666

issn

1096-0023

pii

S1043466603002710

journal_volume

24

pub_type

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