Authors:	Maus, Frank Sakry, Dominik Binamé, Fabien Karram, Khalad Rajalingam, Krishnaraj Watts, Colin Heywood, Richard Krüger, Rejko Stegmüller, Judith Werner, Hauke B. Nave, Klaus-Armin Albers, Eva-Maria Trotter, Jacqueline
Title:	The NG2 proteoglycan protects oligodendrocyte precursor cells against oxidative stress via interaction with OMI/HtrA2
Online publication date:	17-Oct-2022
Year of first publication:	2015
Language:	english
Abstract:	The NG2 proteoglycan is characteristically expressed by oligodendrocyte progenitor cells (OPC) and also by aggressive brain tumours highly resistant to chemo- and radiation therapy. Oligodendrocyte-lineage cells are particularly sensitive to stress resulting in cell death in white matter after hypoxic or ischemic insults of premature infants and destruction of OPC in some types of Multiple Sclerosis lesions. Here we show that the NG2 proteoglycan binds OMI/HtrA2, a mitochondrial serine protease which is released from damaged mitochondria into the cytosol in response to stress. In the cytosol, OMI/HtrA2 initiates apoptosis by proteolytic degradation of anti-apoptotic factors. OPC in which NG2 has been downregulated by siRNA, or OPC from the NG2-knockout mouse show an increased sensitivity to oxidative stress evidenced by increased cell death. The proapoptotic protease activity of OMI/HtrA2 in the cytosol can be reduced by the interaction with NG2. Human glioma expressing high levels of NG2 are less sensitive to oxidative stress than those with lower NG2 expression and reducing NG2 expression by siRNA increases cell death in response to oxidative stress. Binding of NG2 to OMI/HtrA2 may thus help protect cells against oxidative stress-induced cell death. This interaction is likely to contribute to the high chemo- and radioresistance of glioma.
DDC:	570 Biowissenschaften 570 Life sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8053
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	PLoS one 10 9
Pages or article number:	e0137311
Publisher:	PLoS
Publisher place:	Lawrence, Kan.
Issue date:	2015
ISSN:	1932-6203
Publisher URL:	http://dx.doi.org/10.1371/journal.pone.0137311
Publisher DOI:	10.1371/journal.pone.0137311
Annotation:	Albers, Eva-Maria veröffentlicht auch unter Krämer-Albers, Eva-Maria
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)