Exposure of Cultured Astrocytes to Menadione Triggers Rapid Radical Formation, Glutathione Oxidation and Mrp1-Mediated Export of Glutathione Disulfide

Neurochemical Research
Johann Steinmeier, Ralf Dringen

Abstract

Menadione (2-methyl-1,4-naphthoquinone) is a synthetic derivative of vitamin K that allows rapid redox cycling in cells and thereby generates reactive oxygen species (ROS). To test for the consequences of a treatment of brain astrocytes with menadione, we incubated primary astrocyte cultures with this compound. Incubation with menadione in concentrations of up to 30 µM did not affect cell viability. In contrast, exposure of astrocytes to 100 µM menadione caused a time-dependent impairment of cellular metabolism and cell functions as demonstrated by impaired glycolytic lactate production and strong increases in the activity of extracellular lactate dehydrogenase and in the number of propidium iodide-positive cells within 4 h of incubation. In addition, already 5 min after exposure of astrocytes to menadione a concentration-dependent increase in the number of ROS-positive cells as well as a concentration-dependent and transient accumulation of cellular glutathione disulfide (GSSG) were observed. The rapid intracellular GSSG accumulation was followed by an export of GSSG that was prevented in the presence of MK571, an inhibitor of the multidrug resistance protein 1 (Mrp1). Menadione-induced glutathione (GSH) oxidation and ROS form...Continue Reading

References

Jan 1, 1985·Methods in Enzymology·B Hamprecht, F Löffler
Oct 1, 1985·Chemico-biological Interactions·D RossP Moldeus
Aug 1, 1996·Biochemical Society Transactions·S PeuchenJ B Clark
Dec 1, 1996·Japanese Journal of Pharmacology·K Abe, H Saito
Oct 21, 1998·Developmental Neuroscience·R Dringen, B Hamprecht
Jul 6, 2000·Progress in Neurobiology·R Dringen
Jul 13, 2000·Free Radical Biology & Medicine·S B HollensworthS P LeDoux
Mar 6, 2004·Pharmacological Reviews·Martijn RooseboomNico P E Vermeulen
Apr 22, 2004·Alcoholism, Clinical and Experimental Research·B GonthierL Barret
Dec 2, 2004·Journal of Neuroscience Research·Ralf DringenJohannes Hirrlinger
Mar 27, 2007·Free Radical Biology & Medicine·Glenda M BishopStephen R Robinson
Apr 22, 2008·Biochemical and Biophysical Research Communications·Takahito NishiyamaAkira Hiratsuka
Nov 13, 2008·Antioxidants & Redox Signaling·Nicolas BrandesUrsula Jakob
Apr 22, 2009·Journal of Neuroscience Research·Jeff R LiddellRalf Dringen
Jan 26, 2010·Neurochemistry International·Maike M Schmidt, Ralf Dringen
Feb 16, 2010·Archives of Biochemistry and Biophysics·Viola KlausLars-Oliver Klotz
Apr 7, 2010·Archives of Biochemistry and Biophysics·Albena T Dinkova-Kostova, Paul Talalay
Sep 29, 2012·Neurochemistry International·Ketki TulpuleRalf Dringen
Oct 6, 2012·Biochimica Et Biophysica Acta·Marcel Deponte
Sep 19, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lars-Oliver KlotzClaus Jacob
Oct 31, 2014·Journal of Neuroscience Research·Michaela C HohnholtRalf Dringen
Nov 28, 2014·Neurochemical Research·Ralf DringenEva-Maria Blumrich
Mar 1, 2016·Free Radical Biology & Medicine·Narciso CoutoJill Barber
Apr 26, 2017·Annual Review of Biochemistry·Helmut SiesDean P Jones

❮ Previous
Next ❯

Citations

Apr 26, 2021·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Ahmed I El-BatalFarag M Mosallam

❮ Previous
Next ❯

Software Mentioned

- Elements BR
ImageJ
NIS

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.