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1 Departments of Physiology, Pediatrics, and Obstetrics & Gynecology and 2 Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163; and 3 Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia 194064
We investigated the relationships among
expression, activity, and spatial organization of cyclooxygenase (COX-1
and COX-2) in endothelial cells from porcine and human cerebral
microvessels and from human umbilical vein. In quiescent cells, COX-1
was detected in the perinuclear zone and the cytoplasm, while COX-2 was
mainly a nuclear resident possibly connected with the nuclear matrix. COX-2 immunogold labeling was situated in the nuclear envelope, at the
nuclear pores, and in connection with the perichromatin regions of the
nucleus, considered to be the sites of active transcription. In human
endothelial cells transcriptionally activated by interleukin (IL)-1
,
the nucleus remained a major COX-2 localization site during the first
12 h of stimulation, when COX-2 expression was maximally induced.
The continuous rise in prostanoid synthesis at 17-23 h of
stimulation was associated with COX-2 relocation from the nucleus to
the nuclear envelope and the cytoplasm. IL-1
did not affect COX-1
expression, activity, and localization. COX-2 nuclear localization
sites and trafficking between the nucleus and the cytoplasm in
endothelial cells may indicate a novel function of COX-2 in regulating
gene expression.
prostanoids; endothelial cell; interleukin-1
; nucleus
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