Merck

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

PloS one (2015-09-05)
Frank Maus, Dominik Sakry, Fabien Binamé, Khalad Karram, Krishnaraj Rajalingam, Colin Watts, Richard Heywood, Rejko Krüger, Judith Stegmüller, Hauke B Werner, Klaus-Armin Nave, Eva-Maria Krämer-Albers, Jacqueline Trotter
RESUMEN

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.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, 98%
Sigma-Aldrich
N,N-Dimethylformamide, for molecular biology, ≥99%
Sigma-Aldrich
Hydrogen peroxide solution, 34.5-36.5%
Sigma-Aldrich
Hydrogen peroxide solution, 30 % (w/w) in H2O, contains stabilizer
Sigma-Aldrich
MISSION® esiRNA, targeting human CSPG4
Sigma-Aldrich
Lithium acetate, 99.95% trace metals basis
Sigma-Aldrich
Hydrogen peroxide solution, contains potassium stannate as inhibitor, 30-32 wt. % in water, semiconductor grade, 99.999% trace metals basis
Sigma-Aldrich
N,N-Dimethylformamide, ACS reagent, ≥99.8%
Sigma-Aldrich
N,N-Dimethylformamide, anhydrous, 99.8%
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Vcan
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Rnf5
Sigma-Aldrich
Anti-HTRA2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
N,N-Dimethylformamide, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Adenosine 5′-diphosphoribose sodium salt, ≥93%
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
SAFC
L-Glutamine
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
L-Glutamine