Hypoxic stress upregulates Kir 2.1 expression by a pathway including hypoxic-inducible factor-1α and dynamin2 in brain capillary endothelial cells

American Journal of Physiology. Cell Physiology
Hideto YamamuraYuji Imaizumi

Abstract

Brain capillary endothelial cells (BCECs) play a central role in maintenance of blood-brain barrier (BBB) function and, therefore, are essential for central nervous system homeostasis and integrity. Although brain ischemia damages BCECs and causes disruption of BBB, the related influence of hypoxia on BCECs is not well understood. Hypoxic stress can upregulate functional expression of specific K+ currents in endothelial cells, e.g., Kir2.1 channels without any alterations in the mRNA level, in t-BBEC117, a cell line derived from bovine BCECs. The hyperpolarization of membrane potential due to Kir2.1 channel upregulation significantly facilitates cell proliferation. In the present study, the mechanisms underlying the hypoxia-induced Kir2.1 upregulation was examined. We emphasize the involvement of dynamin2, a protein known to be involved in a number of surface expression pathways. Hypoxic culture upregulated dynamin2 expression in t-BBEC117 cells. The inhibition of dynamin2 by Dynasore canceled hypoxia-induced upregulation of Kir2.1 currents by reducing surface expression. On the contrary, Kir2.1 currents and proteins in t-BBEC117 cultured under normoxia were increased by overexpression of dynamin2, but not by dominant-negative ...Continue Reading

References

May 1, 1992·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R E ten EickH H Rasmussen
Mar 1, 1997·The American Journal of Physiology·C W LefflerH Parfenova
Mar 12, 1999·Journal of Molecular and Cellular Cardiology·I Fleming, R Busse
May 18, 2001·American Journal of Physiology. Heart and Circulatory Physiology·K A Dora, C J Garland
Oct 3, 2001·Physiological Reviews·B Nilius, G Droogmans
Nov 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D M StrokaD Candinas
Oct 11, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Amanda W WyattGiovanni E Mann
Aug 19, 2003·The Journal of Biological Chemistry·Rubén VicenteAntonio Felipe
Apr 13, 2004·American Journal of Physiology. Cell Physiology·Rachel C BrownThomas P Davis
Jan 18, 2005·Biochemical and Biophysical Research Communications·Rachel C Brown, Thomas P Davis
Jan 18, 2005·American Journal of Physiology. Heart and Circulatory Physiology·L ChiltonW R Giles
May 26, 2005·Pharmacological Reviews·Brian T Hawkins, Thomas P Davis
Dec 24, 2005·Nature Reviews. Neuroscience·N Joan AbbottElisabeth Hansson
Jun 3, 2006·Developmental Cell·Eric MaciaTomas Kirchhausen
Aug 12, 2006·The EMBO Journal·Jamel MankouriAsipu Sivaprasadarao
Feb 26, 2008·Biochemical and Biophysical Research Communications·Hyung Gyun KimHye Gwang Jeong
Apr 16, 2008·Journal of Cell Science·Karin HåbergSven R Carlsson
Apr 26, 2008·Pflügers Archiv : European journal of physiology·Won Sun ParkYung E Earm
Feb 21, 2009·Stroke; a Journal of Cerebral Circulation·Purnima NarasimhanPak H Chan
Oct 8, 2009·The Journal of Clinical Investigation·Alexander WeidemannRandall S Johnson
Jan 21, 2010·Physiological Reviews·Hiroshi HibinoYoshihisa Kurachi
Jul 6, 2011·Biochemical and Biophysical Research Communications·Hiroaki KitoYuji Imaizumi
Dec 3, 2011·The Journal of Biological Chemistry·Ameet A ChimoteLaura Conforti
Nov 30, 2012·Pflügers Archiv : European journal of physiology·Rosanne VarkevisserMarcel A G van der Heyden
Feb 2, 2013·Central Nervous System Agents in Medicinal Chemistry·Baowan Lin
Apr 18, 2013·Nature Communications·Kannan AlpadiChristopher Peters
Aug 29, 2013·Traffic·Sanja SeverChangkyu Gu
Sep 26, 2013·Frontiers in Endocrinology·Arlek M González-JamettAna María Cárdenas
Nov 15, 2013·Molecular Biology of the Cell·Alexander R KolbJeffrey L Brodsky
Mar 20, 2014·British Journal of Pharmacology·S EngelhardtO O Ogunshola
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Hemant P JoshiSundaram Ramakrishnan
Aug 6, 2014·Journal of Cellular and Molecular Medicine·Dan ShiYi-Han Chen
Mar 10, 2015·Biochemical and Biophysical Research Communications·Hiroaki KitoYuji Imaizumi
Nov 7, 2015·Cellular and Molecular Life Sciences : CMLS·Ramón Martínez-MármolAntonio Felipe
Feb 4, 2016·The Journal of Physiology·Swapnil K SonkusareMark T Nelson

❮ Previous
Next ❯

Citations

Nov 12, 2019·Cardiovascular Research·Christian StaehrVladimir V Matchkov

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
transfection
fluorescence imaging
confocal microscopy
GTPase
co-IP

Software Mentioned

Dynasore

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.