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Angiotensin receptor type 1 blockade in astrocytes decreases hypoxia-induced cytotoxicity and inflammation

Danielyan, L. and Lourhmati, A. and Verleysdonk, S. and Proksch, B. and Umbreen, S. and Schmidt, B. and Gleiter, C. H. (2007):
Angiotensin receptor type 1 blockade in astrocytes decreases hypoxia-induced cytotoxicity and inflammation.
In: Neurochemical Research, Springer, pp. 1489-1498, 32, (9), ISSN 1573-6903, DOI: 10.1007/s11064-007-9337-6, [Article]

Abstract

The present study investigated the role of angiotensin receptors (AT-R) in the survival and inflam- matory response of astroglia upon hypoxic injury. Expo- sure of rat astroglial primary cultures (APC) to hypoxic conditions (HC) led to decreased viability of the cells and to a 3.5-fold increase in TNF-alpha release. AT-R type1 (AT1-R) antagonist losartan and its metabolite EXP3174 decrease the LDH release (by 36 ± 9%; 45 ± 6%) from APC under HC. Losartan diminished TNF-alpha release (by 40 ± 15%) and the number of TUNEL-cells by 204 ± 38% under HC, alone and together with angiotensin II (ATII), while EXP3174 was dependent on ATII for its effect on TNF-alpha. The AT2-R antagonist, PD123.319, did not influence the release of LDH and TNF-alpha under normoxic (NC) and HC. These data suggest that AT1-R may decrease the susceptibility of astrocytes to hypoxic injury and their propensity to release TNF-alpha. AT1-R antagonists may therefore be of therapeutic value during hypoxia-associated neurodegeneration.

Item Type: Article
Erschienen: 2007
Creators: Danielyan, L. and Lourhmati, A. and Verleysdonk, S. and Proksch, B. and Umbreen, S. and Schmidt, B. and Gleiter, C. H.
Title: Angiotensin receptor type 1 blockade in astrocytes decreases hypoxia-induced cytotoxicity and inflammation
Language: English
Abstract:

The present study investigated the role of angiotensin receptors (AT-R) in the survival and inflam- matory response of astroglia upon hypoxic injury. Expo- sure of rat astroglial primary cultures (APC) to hypoxic conditions (HC) led to decreased viability of the cells and to a 3.5-fold increase in TNF-alpha release. AT-R type1 (AT1-R) antagonist losartan and its metabolite EXP3174 decrease the LDH release (by 36 ± 9%; 45 ± 6%) from APC under HC. Losartan diminished TNF-alpha release (by 40 ± 15%) and the number of TUNEL-cells by 204 ± 38% under HC, alone and together with angiotensin II (ATII), while EXP3174 was dependent on ATII for its effect on TNF-alpha. The AT2-R antagonist, PD123.319, did not influence the release of LDH and TNF-alpha under normoxic (NC) and HC. These data suggest that AT1-R may decrease the susceptibility of astrocytes to hypoxic injury and their propensity to release TNF-alpha. AT1-R antagonists may therefore be of therapeutic value during hypoxia-associated neurodegeneration.

Journal or Publication Title: Neurochemical Research
Volume: 32
Number: 9
Publisher: Springer
Divisions: 07 Department of Chemistry
Date Deposited: 20 Nov 2008 08:26
DOI: 10.1007/s11064-007-9337-6
License: [undefiniert]
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