Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P21817 (
RyR1
)
1,154
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Spinal cord injury (SCI) results in marked atrophy and dysfunction of skeletal muscle. There are currently no effective treatments for SCI-induced muscle atrophy or the dysfunction of the remaining muscle tissue.
Nicotinamide adenine dinucleotide phosphate
(
NADPH
) oxidase-4 (Nox4) produces reactive oxygen species (ROS) in sarcoplasmic reticulum (SR) and has been identified as an important O
2
sensor in skeletal muscle. Ryanodine receptors (RyRs) are calcium (Ca
2+
) channels that are responsible for Ca
2+
release from SR. In skeletal muscle, type1 RyR (
RyR1
) is predominantly functional.
RyR1
is regulated by multiple proteins, including calstabin1, which assures that they close appropriately once contraction has ceased.
RyR1
function is also regulated by oxidation and redox-dependent cysteine nitrosylation. Excessive oxidation/nitrosylation of
RyR1
is associated with dissociation of calstabin1 and reduced muscle force generation. However, whether Nox4 levels in skeletal muscle are elevated or whether
RyR1
is oxidized or nitrosylated after SCI has not been determined. In this study, we examined Nox4 expression, oxidation/nitrolysation status, and association of calstabin1 with
RyR1
in skeletal muscle derived from rats that were subjected to T4 complete transection (SCI), and observed elevated expression of Nox4 messenger RNA and protein in muscle after SCI associated with enhanced binding of Nox4 to
RyR1
, increased oxidation and nitrosylation of
RyR1
, and dissociation of calstabin1 from
RyR1
in SCI rat muscle. Our data suggest that
RyR1
dysfunction resulting from excessive oxidation/nitrosylation may contribute to reduced specific force after SCI and suggest that Nox4 may be the source of ROS responsible for increased oxidation and nitrosylation of
RyR1
.
...
PMID:Spinal Cord Injury Leads to Hyperoxidation and Nitrosylation of Skeletal Muscle Ryanodine Receptor-1 Associated with Upregulation of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4. 2799
