Medizinische Universität Graz - Research portal

Navigation/Search

• Researchers.
• Institutions.
• Projects.
• Publications.
• Partners.
• Sponsors.
• Equipment.
• Knowhow.
• Fields of Research.

"Faces" of the day:

Katharina Jandl

Nina Höller

Nariae Baik-Schneditz

Ellen Heitzer

Marianne Brodmann

Ewald Kolesnik

Bernhard Schwaberger

Maximilian Seles

Gabor Toth-Gayor

Lukas Peter Mileder

Niels Hammer

Christian Josef Hill

Christian Viertler

Philipp Klaritsch

Daniel Scherr

Harald Köfeler

Gerhard Pichler

Roland Malli

Michael Fuchsjäger

Gernot Plank

Peter Fickert

Richard Zigeuner

Peter Holzer

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Waldeck-Weiermair, M; Yadav, S; Kaynert, J; Thulabandu, VR; Pandey, AK; Spyropoulos, F; Covington, T; Das, AA; Kruger, C; Michel, T.
Differential endothelial hydrogen peroxide signaling via Nox isoforms: Critical roles for Rac1 and modulation by statins
REDOX BIOL. 2022; 58: 102539 Doi: 10.1016/j.redox.2022.102539 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Leading authors Med Uni Graz

Waldeck-Weiermair Markus

Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Abstract:

Statins have manifold protective effects on the cardiovascular system. In addition to lowering LDL cholesterol levels, statins also have antioxidant effects on cardiovascular tissues involving intracellular redox pathways that are incompletely understood. Inhibition of HMG-CoA reductase by statins not only modulates cholesterol syn-thesis, but also blocks the synthesis of lipids necessary for the post-translational modification of signaling pro-teins, including the GTPase Rac1. Here we studied the mechanisms whereby Rac1 and statins modulate the intracellular oxidant hydrogen peroxide (H2O2) via NADPH oxidase (Nox) isoforms. In live-cell imaging exper-iments using the H2O2 biosensor HyPer7, we observed robust H2O2 generation in human umbilical vein endo-thelial cells (HUVEC) following activation of cell surface receptors for histamine or vascular endothelial growth factor (VEGF). Both VEGF-and histamine-stimulated H2O2 responses were abrogated by siRNA-mediated knockdown of Rac1. VEGF responses required the Nox isoforms Nox2 and Nox4, while histamine-stimulated H2O2 signals are independent of Nox4 but still required Nox2. Endothelial H2O2 responses to both histamine and VEGF were completely inhibited by simvastatin. In resting endothelial cells, Rac1 is targeted to the cell membrane and cytoplasm, but simvastatin treatment promotes translocation of Rac1 to the cell nucleus. The effects of simvastatin both on receptor-dependent H2O2 production and Rac1 translocation are rescued by treatment of cells with mevalonic acid, which is the enzymatic product of the HMG-CoA reductase that is inhibited by statins. Taken together, these studies establish that receptor-modulated H2O2 responses to histamine and VEGF involve distinct Nox isoforms, both of which are completely dependent on Rac1 prenylation.

Find related publications in this database (Keywords)

Endothelial cells

Oxidative stress

Statins

Rac1

Signal transduction

NADPH oxidases

© Med Uni Graz • Imprint