The NG2 Proteoglycan Protects Oligodendrocyte Precursor Cells against Oxidative Stress via Interaction with OMI/HtrA2

PloS One
Frank MausJacqueline Trotter

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 st...Continue Reading

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Citations

Jun 30, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Nina SchultzMalin Wennström
May 17, 2017·Antioxidants & Redox Signaling·Madalina-Viviana NastaseLiliana Schaefer
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Dec 17, 2017·Oncotarget·Xuetao HanGe Zhang
Apr 25, 2018·Journal of Experimental & Clinical Cancer Research : CR·Le TangZhaoyang Zeng
Dec 15, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Elisa TamburiniRoberto Perris
Sep 13, 2018·Reviews in the Neurosciences·Xiao Juan SuDezhi Mu
Mar 22, 2021·Fluids and Barriers of the CNS·Francesco GirolamoDaniela Virgintino

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Methods Mentioned

BETA
Two
two-hybrid
protease assay
Fluorescence
transfection
ELISA
Assay
electrophoresis
two hybrid
Y2H

Software Mentioned

ImageJ
Photoshop

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