Dynamics of nuclear localization sites for COX-2 in vascular endothelial cells.
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)-1beta, 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-1beta 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.
Parfenova
H
H
Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. hparf@physio1.utmem.edu
Parfenov
V N
VN
Shlopov
B V
BV
Levine
V
V
Falkos
S
S
Pourcyrous
M
M
Leffler
C W
CW
D000818:Animals; D002196:Capillaries / Q000201:enzymology; D002467:Cell Nucleus / Q000737:chemistry / Q000201:enzymology*; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D006801:Humans; D015151:Immunoblotting; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D010741:Phospholipases A / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013687:Telencephalon / Q000098:blood supply; D014471:Umbilical Veins / Q000166:cytology; D014841:von Willebrand Factor / Q000276:immunology
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D020033:Protein Isoforms; D014841:von Willebrand Factor; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A