PMID: 12788228Jun 6, 2003Paper

Menadione causes endothelial barrier failure by a direct effect on intracellular thiols, independent of reactive oxidant production

Biochimica Et Biophysica Acta
W C McAmisMatthew B Wolf

Abstract

Menadione (MQ), a quinone used with cancer chemotherapeutic agents, causes cytotoxicity to endothelial cells (EC). Previous studies have suggested that MQ induces an oxidative stress and dysfunction in EC by either increasing hydrogen peroxide (H(2)O(2)) production or depleting intracellular glutathione (GSH), the main intracellular antioxidant. Since a primary function of EC is to form a barrier to fluid movement into tissues, protecting organs from edema formation and dysfunction, our aim was to see if MQ would cause a barrier dysfunction and to ascertain the mechanism. Using diffusional permeability to fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) as a measure of barrier function, we found that 15 micro M MQ incubated with a bovine pulmonary artery EC (BPAEC) monolayer for 4 h produced a profound barrier failure ( approximately 7-fold increase in permeability) with a parallel fall in glutathione, almost to depletion. These two events were highly correlated. Immunofluorescent imaging showed formation of paracellular holes consistent with a loss or rearrangement of cell-cell and cell-matrix adhesion molecules. H(2)O(2) (100 micro M), a concentration which gave about the same increase in permeability as MQ,...Continue Reading

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Citations

Jul 18, 2006·Cell Biology and Toxicology·Y IbukiR Goto
Jul 1, 2014·Microvascular Research·Derek B J BoneJames R Hammond
Jun 6, 2006·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Matthew B Wolf, John W Baynes
Feb 23, 2007·Birth Defects Research. Part C, Embryo Today : Reviews·Jason M Hansen
Dec 13, 2005·Biochimica Et Biophysica Acta·Matthew B Wolf, John W Baynes
Jan 29, 2010·The Biochemical Journal·Jolanta Idkowiak-BaldysYusuf A Hannun
Aug 2, 2008·The Journal of Biological Chemistry·Marcelo A CominiR Luise Krauth-Siegel
Apr 13, 2004·American Journal of Physiology. Cell Physiology·Peter J KuhlencordtPaul L Huang
Jan 23, 2016·The Journal of Biological Chemistry·John A CollinsRichard F Loeser
Aug 20, 2019·Vascular Pharmacology·Anna BarStefan Chlopicki
Jun 22, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Roberto CampagnaStefan Chlopicki
Nov 24, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Ewelina BikKatarzyna Majzner
Mar 6, 2008·Journal of Medicinal Chemistry·Sanjeev KumarAlexander J Muller

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