Journal Article

DZNE-2020-04413

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The NG2 Proteoglycan Protects Oligodendrocyte Precursor Cells against Oxidative Stress via Interaction with OMI/HtrA2.

Maus, F. ; Sakry, D. ; Binamé, F. ; Karram, K. ; Rajalingam, K. ; Watts, C. ; Heywood, R. ; Krüger, R.DZNE* ; Stegmüller, J. ; Werner, H. B. ; Nave, K.-A. ; Krämer-Albers, E.-M. ; Trotter, J.

2015
PLOS San Francisco, California, US

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Please use a persistent id in citations: doi:10.1371/journal.pone.0137311

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.

Keyword(s): Animals (MeSH) ; Antibodies, Neutralizing: pharmacology (MeSH) ; Antigens: genetics (MeSH) ; Antigens: metabolism (MeSH) ; Apoptosis: drug effects (MeSH) ; Brain Neoplasms: genetics (MeSH) ; Brain Neoplasms: metabolism (MeSH) ; Brain Neoplasms: pathology (MeSH) ; Cell Line, Tumor (MeSH) ; Cerebellum: drug effects (MeSH) ; Cerebellum: metabolism (MeSH) ; Cerebellum: pathology (MeSH) ; Cytosol: drug effects (MeSH) ; Cytosol: metabolism (MeSH) ; Gene Expression Regulation, Neoplastic (MeSH) ; Glioblastoma: genetics (MeSH) ; Glioblastoma: metabolism (MeSH) ; Glioblastoma: pathology (MeSH) ; High-Temperature Requirement A Serine Peptidase 2 (MeSH) ; Humans (MeSH) ; Hydrogen Peroxide: pharmacology (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Mitochondria: drug effects (MeSH) ; Mitochondria: metabolism (MeSH) ; Mitochondrial Proteins: genetics (MeSH) ; Mitochondrial Proteins: metabolism (MeSH) ; Oxidative Stress (MeSH) ; Primary Cell Culture (MeSH) ; Protein Binding (MeSH) ; Proteoglycans: antagonists & inhibitors (MeSH) ; Proteoglycans: genetics (MeSH) ; Proteoglycans: metabolism (MeSH) ; RNA, Small Interfering: genetics (MeSH) ; RNA, Small Interfering: metabolism (MeSH) ; Serine Endopeptidases: genetics (MeSH) ; Serine Endopeptidases: metabolism (MeSH) ; Signal Transduction (MeSH) ; Antibodies, Neutralizing ; Antigens ; Mitochondrial Proteins ; Proteoglycans ; RNA, Small Interfering ; chondroitin sulfate proteoglycan 4 ; Hydrogen Peroxide ; Serine Endopeptidases ; HTRA2 protein, human ; High-Temperature Requirement A Serine Peptidase 2 ; Htra2 protein, mouse

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser 1)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2015

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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