Am J Physiol Cell Physiol Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 277: C1066-C1074, 1999;
0363-6143/99 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (31)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Park, J. H.
Right arrow Articles by Alexander, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Park, J. H.
Right arrow Articles by Alexander, J. S.
Vol. 277, Issue 6, C1066-C1074, December 1999

EDITORIAL FOCUS
Hypoxia/aglycemia increases endothelial permeability: role of second messengers and cytoskeleton

J. H. Park, N. Okayama, D. Gute, A. Krsmanovic, H. Battarbee, and J. S. Alexander

Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3932

The effects of hypoxia/aglycemia on microvascular endothelial permeability were evaluated, and the second messenger systems and the cytoskeletal-junctional protein alterations in this response were also examined. Monolayers of human dermal microvascular endothelial cells on microcarrier beads were exposed to either thioglycolic acid (5 mM, an O2 chelator), glucose-free medium, or both stresses together. Permeability measurements were performed over a 90-min time course. Although neither hypoxia alone nor aglycemia alone increased endothelial permeability significantly, the combination of both increased significantly as early as 15 min. Intracellular Ca2+ measurements with fura 2-AM showed that hypoxia/aglycemia treatment increased Ca2+ influx. To determine the second messengers involved in increased permeability, monolayers were incubated for 30 min with the cytosolic Ca2+ scavenger 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8, 0.1 mM), a classical protein kinase C (PKC) blocker, Gö-6976 (10 nM), a cGMP-dependent protein kinase (PKG) antagonist, KT-5823 (0.5 µM), or the mitogen-activated protein (MAP) kinase inhibitor PD-98059 (20 µM). Hypoxia/aglycemia-mediated permeability changes were blocked by chelating cell Ca2+, PKC blockade, PKG blockade, and by inhibiting p38 MAP kinase-1. Finally, changes in the binding of junctional proteins to the cytoskeleton under the same conditions were assessed. The concentrations of occludin and pan-reactive cadherin binding to the cytoskeleton were significantly decreased by only both stresses together. However, these effects were also blocked by pretreatment with TMB-8, Gö-6976, KT-5823 (not in occludin), and PD-98059. These data suggest that hypoxia/aglycemia-mediated endothelial permeability may occur through PKC, PKG, MAP kinase, and Ca2+ related to dissociation of cadherin-actin and occludin-actin junctional bonds.

thioglycollate; oxygen; glucose; microvasculature; junction


This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Therade-Matharan, E. Laemmel, S. Carpentier, Y. Obata, T. Levade, J. Duranteau, and E. Vicaut
Reactive oxygen species production by mitochondria in endothelial cells exposed to reoxygenation after hypoxia and glucose depletion is mediated by ceramide
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1756 - R1762.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Therade-Matharan, E. Laemmel, J. Duranteau, and E. Vicaut
Reoxygenation after hypoxia and glucose depletion causes reactive oxygen species production by mitochondria in HUVEC
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1037 - R1043.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
R. C. Brown, K. S. Mark, R. D. Egleton, and T. P. Davis
Protection against hypoxia-induced blood-brain barrier disruption: changes in intracellular calcium
Am J Physiol Cell Physiol, May 1, 2004; 286(5): C1045 - C1052.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. S. Powell, M. M. Wright, and R. M. Jackson
p38mapk and MEK1/2 inhibition contribute to cellular oxidant injury after hypoxia
Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L826 - L833.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y.-S. Nan, G.-G. Feng, Y. Hotta, K. Nishiwaki, Y. Shimada, A. Ishikawa, N. Kurimoto, T. Shigei, and N. Ishikawa
Neuropeptide Y enhances permeability across a rat aortic endothelial cell monolayer
Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1027 - H1033.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Siflinger-Birnboim and A. Johnson
Protein kinase C modulates pulmonary endothelial permeability: a paradigm for acute lung injury
Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L435 - L451.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
C. Li and R. M. Jackson
Reactive species mechanisms of cellular hypoxia-reoxygenation injury
Am J Physiol Cell Physiol, February 1, 2002; 282(2): C227 - C241.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online