Transcriptional regulation of endothelial constitutive pghs-1
expression by phorbol ester.
Xu, Xiao-Ming, Jih-Luh Tang, Asghar Hajibeigi, David S. Loose
-Mitchell, and Kenneth K. Wu.
Vascular Biology Research Center and Division of Hematology,
Departments of Internal Medicine and Pharmacology, The University of
Texas Houston Health Science Center, Houston, Texas 77030
APStracts 2:0261C, 1995.
Human endothelial cells (EC) contain two isoforms of prostaglandin H
synthase (PGHS). PGHS-1 is constitutively expressed whereas PGHS-2 is
inducible. To determine whether expression of PGHS-1 is regulated, we
treated cultured human umbilical vein EC (HUVEC) with phorbol 12
-myristate 13-acetate (PMA) or its inactive analog and measured PGHS-1
mRNA levels by Northern analysis and competitive polymerase chain
reaction. PMA increased PGHS-1 mRNA levels determined by both
techniques in a time- and concentration-dependent manner. The mRNA
level was increased about 2-fold over the basal level after 4-6 h of
PMA (10-50 nM) treatment. The level of PGHS-1 protein was similarly
increased by PMA. Stimulation of PGHS-1 mRNA levels was abrogated by
cycloheximide, actinomycin D, staurosporine or calphostin C. The 5'
-promoter activity of human PGHS-1 gene was increased by 2-fold over
the basal level by PMA in NS-20 cells. These results indicate that
the constitutive PGHS-1 in HUVEC is transcriptionally stimulated by
PMA in a protein kinase C dependent manner.
Received 12 January 1995; accepted in final form 5 July 1995.
APS Manuscript Number C29-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.