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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Antioxid+Redox+Signal
2011 ; 14
(10
): 1815-27
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gab.com Text
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English Wikipedia
Pathophysiologically relevant levels of hydrogen peroxide induce
glutamate-independent neurodegeneration that involves activation of transient
receptor potential melastatin 7 channels
#MMPMID20812867
Coombes E
; Jiang J
; Chu XP
; Inoue K
; Seeds J
; Branigan D
; Simon RP
; Xiong ZG
Antioxid Redox Signal
2011[May]; 14
(10
): 1815-27
PMID20812867
show ga
Stroke/brain ischemia is a leading cause of death and long-term disabilities.
Increased oxidative stress plays an important role in the pathology of brain
ischemia. Hydrogen peroxide (H(2)O(2)) is a major oxidant known to cause neuronal
injury; however, the detailed mechanism remains unclear. Previous studies have
suggested that H(2)O(2)-induced injury is associated with increased intracellular
Ca(2+), mediated by glutamate receptors or voltage-gated Ca(2+) channels. Here,
we demonstrate that, at concentrations relevant to stroke, H(2)O(2) induces a
Ca(2+)-dependent injury of mouse cortical neurons in the absence of activation of
these receptors/channels. With the culture medium containing blockers of
glutamate receptors and voltage-gated Ca(2+) channels, brief exposure of neurons
to H(2)O(2) induced a dose-dependent injury. Reducing [Ca(2+)](e) inhibited
whereas increasing [Ca(2+)](e) potentiated the H(2)O(2) injury. Fluorescent
Ca(2+) imaging confirmed the increase of [Ca(2+)](i) by H(2)O(2) in the presence
of the blockers of glutamate receptors and voltage-gated Ca(2+) channels.
Addition of 2-aminoethoxydiphenyl borate, an inhibitor of transient receptor
potential melastatin 7 (TRPM7) channels, or the use of TRPM7-small interference
RNA, protected the neurons from H(2)O(2) injury. In contrast, overexpressing
TRPM7 channels in human embryonic kidney 293 cells increased H(2)O(2) injury. Our
findings indicate that H(2)O(2) can induce Ca(2+) toxicity independent of
glutamate receptors and voltage-gated Ca(2+) channels. Activation of TRPM7
channels is involved in such toxicity.