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Hypoosmotic swelling increases protein tyrosine nitration in cultured rat astrocytes
Author(s) -
Schliess Freimut,
Foster Natalie,
Görg Boris,
Reinehr Roland,
Häussinger Dieter
Publication year - 2004
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20019
Subject(s) - astrocyte , biology , egta , peroxynitrite , nmda receptor , extracellular , superoxide dismutase , biochemistry , tyrosine , catalase , nitric oxide , calmodulin , oxidative stress , superoxide , medicine , microbiology and biotechnology , endocrinology , receptor , calcium , central nervous system , enzyme
Astrocyte swelling is observed in different types of brain injury. We studied a potential contribution of swelling to protein tyrosine nitration (PTN) by using cultured rat astrocytes exposed to hypoosmotic (205 mosmol/L) medium. Hypoosmolarity (2 h) increases total PTN by about 2‐fold in 2 h. The hypoosmotic PTN is significantly inhibited by the NMDA receptor antagonist MK‐801, the nitric oxide synthase (NOS) inhibitor L ‐NMMA, the extracellular Ca 2+ chelator EGTA and the calmodulin antagonist W13, suggesting the involvement of NMDA receptor activation, influx of extracellular Ca 2+ and Ca 2+ /calmodulin‐dependent NO synthesis. Further, superoxide dismutase plus catalase and uric acid strongly inhibit hypoosmotic PTN, suggesting the involvement of the toxic metabolite peroxynitrite (ONOO − ) as a nitrating agent. Hypoosmotic astrocyte swelling rapidly stimulates generation of reactive oxygen intermediates; this process is prevented by MK‐801 and EGTA. In addition, MK‐801 inhibits the hypoosmotic elevation of [Ca 2+ ] i . The findings support the view that astrocyte swelling as induced, for example, by toxins relevant for hepatic encephalopathy is sufficient to produce oxidative stress and PTN and thus contributes to altered astroglial and neuronal function. © 2004 Wiley‐Liss, Inc.