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@ARTICLE{Maus:138091,
author = {Maus, Frank and Sakry, Dominik and Binamé, Fabien and
Karram, Khalad and Rajalingam, Krishnaraj and Watts, Colin
and Heywood, Richard and Krüger, Rejko and Stegmüller,
Judith and Werner, Hauke B and Nave, Klaus-Armin and
Krämer-Albers, Eva-Maria and Trotter, Jacqueline},
title = {{T}he {NG}2 {P}roteoglycan {P}rotects {O}ligodendrocyte
{P}recursor {C}ells against {O}xidative {S}tress via
{I}nteraction with {OMI}/{H}tr{A}2.},
journal = {PLOS ONE},
volume = {10},
number = {9},
issn = {1932-6203},
address = {San Francisco, California, US},
publisher = {PLOS},
reportid = {DZNE-2020-04413},
pages = {e0137311},
year = {2015},
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.},
keywords = {Animals / Antibodies, Neutralizing: pharmacology /
Antigens: genetics / Antigens: metabolism / Apoptosis: drug
effects / Brain Neoplasms: genetics / Brain Neoplasms:
metabolism / Brain Neoplasms: pathology / Cell Line, Tumor /
Cerebellum: drug effects / Cerebellum: metabolism /
Cerebellum: pathology / Cytosol: drug effects / Cytosol:
metabolism / Gene Expression Regulation, Neoplastic /
Glioblastoma: genetics / Glioblastoma: metabolism /
Glioblastoma: pathology / High-Temperature Requirement A
Serine Peptidase 2 / Humans / Hydrogen Peroxide:
pharmacology / Mice / Mice, Inbred C57BL / Mice, Knockout /
Mitochondria: drug effects / Mitochondria: metabolism /
Mitochondrial Proteins: genetics / Mitochondrial Proteins:
metabolism / Oxidative Stress / Primary Cell Culture /
Protein Binding / Proteoglycans: antagonists $\&$ inhibitors
/ Proteoglycans: genetics / Proteoglycans: metabolism / RNA,
Small Interfering: genetics / RNA, Small Interfering:
metabolism / Serine Endopeptidases: genetics / Serine
Endopeptidases: metabolism / Signal Transduction /
Antibodies, Neutralizing (NLM Chemicals) / Antigens (NLM
Chemicals) / Mitochondrial Proteins (NLM Chemicals) /
Proteoglycans (NLM Chemicals) / RNA, Small Interfering (NLM
Chemicals) / chondroitin sulfate proteoglycan 4 (NLM
Chemicals) / Hydrogen Peroxide (NLM Chemicals) / Serine
Endopeptidases (NLM Chemicals) / HTRA2 protein, human (NLM
Chemicals) / High-Temperature Requirement A Serine Peptidase
2 (NLM Chemicals) / Htra2 protein, mouse (NLM Chemicals)},
cin = {AG Gasser 1},
ddc = {610},
cid = {I:(DE-2719)1210000},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26340347},
pmc = {pmc:PMC4560422},
doi = {10.1371/journal.pone.0137311},
url = {https://pub.dzne.de/record/138091},
}