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Enzyme
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Target Concepts:
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Query: UNIPROT:P21817 (
RyR1
)
1,154
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Status epilepticus
(SE) is a life-threatening emergency that can cause neurodegeneration with debilitating neurological disorders. However, the mechanism by which convulsive SE results in neurodegeneration is not fully understood. It has been shown that epileptic seizures produce markedly increased levels of nitric oxide (NO) in the brain, and that NO induces Ca
2+
release from the endoplasmic reticulum via the type 1 ryanodine receptor (
RyR1
), which occurs through S-nitrosylation of the intracellular Ca
2+
release channel. Here, we show that through genetic silencing of NO-induced activation of the
RyR1
intracellular Ca
2+
release channel, neurons were rescued from seizure-dependent cell death. Furthermore, dantrolene, an inhibitor of
RyR1
, was protective against neurodegeneration caused by SE. These results demonstrate that NO-induced Ca
2+
release via RyR is involved in SE-induced neurodegeneration, and provide a rationale for the use of
RyR1
inhibitors for the prevention of brain damage following SE.
...
PMID:Nitric Oxide-induced Activation of the Type 1 Ryanodine Receptor Is Critical for Epileptic Seizure-induced Neuronal Cell Death. 2754 65
Since the discovery of nitric oxide (NO) as gaseous signaling molecule, two other gaseous mediators, carbon monoxide (CO) and hydrogen sulfide (H
2
S) have been found to be also involved in many physiological and pathophysiological functions. This review will briefly summarize our recent progress in the pathophysiology of NO and H
2
S. In the photoreceptor cells, the level of intracellular Ca
2+
is kept relatively low by H
2
S. Intraperitoneal injection of H
2
S donor to mice protected photoreceptor cells from light-induced retinal degeneration caused by oxidative stress and elevation of intracellular Ca
2+
. Another gaseous mediator NO induces Ca
2+
release from the endoplasmic reticulum via S-nitrosylated type 1 ryanodine receptor (
RyR1
) Ca
2+
release channel. NO-induced Ca
2+
release (NICR) was abolished in primary cultured neurons from the knock-in mice, in which the S-nitrosylation site Cys-3636 of
RyR1
was replaced by Ala (Ryr1
C3636A
). The neurons in hippocampal CA3 region of Ryr1
C3636A
mice were protected against seizure-induced neuronal cell death. The result indicates that NICR is critical for
status epilepticus
-induced neurodegeneration. The developments in the pathophysiology of gaseous mediators in the central nervous system will provide a better pharmacological advances for the treatment of neurodegenerative diseases.
...
PMID:[Pathophysiological functions of gas mediators in neurodegeneration]. 3039 55
