Reference : The NG2 Proteoglycan Protects Oligodendrocyte Precursor Cells against Oxidative Stres...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Life sciences : Genetics & genetic processes
http://hdl.handle.net/10993/22629
The NG2 Proteoglycan Protects Oligodendrocyte Precursor Cells against Oxidative Stress via Interaction with OMI/HtrA2
English
Maus, F. [> >]
Sakry, D. [> >]
Biname, F. [> >]
Karram, K. [> >]
Rajalingam, K. [> >]
Watts, C. [> >]
Heywood, R. [> >]
Krüger, Rejko mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Stegmuller, J. [> >]
Werner, H. B. [> >]
Nave, K. A. [> >]
Kramer-Albers, E. M. [> >]
Trotter, J. [> >]
2015
PLoS ONE
Public Library of Science
10
9
e0137311
Yes (verified by ORBilu)
1932-6203
San Franscisco
CA
[en] 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.
Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
http://hdl.handle.net/10993/22629
10.1371/journal.pone.0137311

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