Connexin 43 Hemichannel Activity Promoted by Pro-Inflammatory Cytokines and High Glucose Alters Endothelial Cell Function

Frontiers in Immunology
Juan C SáezJuan A Orellana

Abstract

The present work was done to elucidate whether hemichannels of a cell line derived from endothelial cells are affected by pro-inflammatory conditions (high glucose and IL-1β/TNF-α) known to lead to vascular dysfunction. We used EAhy 926 cells treated with high glucose and IL-1β/TNF-α. The hemichannel activity was evaluated with the dye uptake method and was abrogated with selective inhibitors or knocking down of hemichannel protein subunits with siRNA. Western blot analysis, cell surface biotinylation, and confocal microscopy were used to evaluate total and plasma membrane amounts of specific proteins and their cellular distribution, respectively. Changes in intracellular Ca2+ and nitric oxide (NO) signals were estimated by measuring FURA-2 and DAF-FM probes, respectively. High glucose concentration was found to elevate dye uptake, a response that was enhanced by IL-1β/TNF-α. High glucose plus IL-1β/TNF-α-induced dye uptake was abrogated by connexin 43 (Cx43) but not pannexin1 knockdown. Furthermore, Cx43 hemichannel activity was associated with enhanced ATP release and activation of p38 MAPK, inducible NO synthase, COX2, PGE2 receptor EP1, and P2X7/P2Y1 receptors. Inhibition of the above pathways prevented completely the incre...Continue Reading

References

Dec 1, 1994·The Journal of Clinical Investigation·U ScherrerP Nicod
Sep 25, 2003·Physiological Reviews·Juan C SaezEric C Beyer
Nov 5, 2003·Nature Reviews. Neuroscience·Daniele Piomelli
Feb 11, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Takashi KuwanoMayumi Ono
Apr 20, 2004·Cardiovascular Research·Rainer Schulz, Gerd Heusch
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Mauricio A RetamalJuan C Sáez
Dec 14, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mauricio A RetamalChristian Giaume
May 2, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jian KangMaiken Nedergaard
Oct 4, 2008·Antioxidants & Redox Signaling·Xavier F Figueroa, Brian R Duling
Jul 17, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Raf PonsaertsGeert Bultynck
Aug 5, 2010·Molecular and Cellular Neurosciences·Nicolas FrogerChristian Giaume
Oct 1, 2010·American Journal of Physiology. Cell Physiology·Kurt A SchalperJuan C Sáez
Oct 22, 2010·American Journal of Physiology. Cell Physiology·Taras LyubchenkoEvgenia V Gerasimovskaya
Sep 6, 2011·European Heart Journal·Ulrich Förstermann, William C Sessa
Dec 14, 2011·American Journal of Physiology. Cell Physiology·Stefanie GödeckeJürgen Schrader
Jan 24, 2012·Biochimica Et Biophysica Acta·Alberto Baroja-MazoPablo Pelegrín
Feb 22, 2012·Brain : a Journal of Neurology·Helen V Danesh-MeyerColin R Green
Jan 12, 2013·Reviews in Endocrine & Metabolic Disorders·Ranganath Muniyappa, James R Sowers
Jul 16, 2013·Progress in Neurobiology·Marijke De BockLuc Leybaert
Jul 31, 2013·Journal of Visualized Experiments : JoVE·Catheleyne D'hondtGeert Bultynck
Nov 19, 2013·Current Molecular Medicine·F MocciaL Munaron
Jan 15, 2014·Journal of Diabetes Research·Romina Hernández-SalinasVictoria Velarde

❮ Previous
Next ❯

Citations

Nov 27, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Adriana VinhasManuela E Gomes
Jan 4, 2021·Cellular and Molecular Life Sciences : CMLS·Raghda RamadanLuc Leybaert
Jan 9, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Damiano BurattoFabio Mammano
Jan 12, 2021·Frontiers in Oncology·Kai-Jun LuoJean X Jiang
Apr 4, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Mauricio A RetamalGuillermo A Altenberg
Apr 4, 2021·International Journal of Molecular Sciences·Jorge González-CasanovaDiana Rojas-Gomez
Apr 4, 2021·International Journal of Molecular Sciences·Raf Van CampenhoutMathieu Vinken
Jun 15, 2021·The EMBO Journal·Oliver KeppLorenzo Galluzzi
Apr 18, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Juan C SáezJuan A Orellana
Aug 8, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Mauricio A RetamalJimmy Stehberg

❮ Previous
Next ❯

Methods Mentioned

BETA
Fluorescence
scraping
electrophoresis
pharmacotherapy

Software Mentioned

METAFLUOR
GraphPad
GraphPad Prism
Origene
IMAGEJ
Excel

Related Concepts

Related Feeds

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.