RGD Reference Report - Spinal Cord Injury Leads to Hyperoxidation and Nitrosylation of Skeletal Muscle Ryanodine Receptor-1 Associated with Upregulation of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4. - Rat Genome Database

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Spinal Cord Injury Leads to Hyperoxidation and Nitrosylation of Skeletal Muscle Ryanodine Receptor-1 Associated with Upregulation of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4.

Authors: Liu, Xin-Hua  Harlow, Lauren  Graham, Zachary A  Bauman, William A  Cardozo, Christopher 
Citation: Liu XH, etal., J Neurotrauma. 2017 Jun 15;34(12):2069-2074. doi: 10.1089/neu.2016.4763. Epub 2017 Feb 27.
RGD ID: 329853757
Pubmed: PMID:27998200   (View Abstract at PubMed)
DOI: DOI:10.1089/neu.2016.4763   (Journal Full-text)

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 O2 sensor in skeletal muscle. Ryanodine receptors (RyRs) are calcium (Ca2+) channels that are responsible for Ca2+ 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Spinal Cord Injuries  ISOFkbp1b (Rattus norvegicus)329853757; 329853757 RGD 
Spinal Cord Injuries  IDA 329853757 RGD 
Spinal Cord Injuries  ISONox4 (Rattus norvegicus)329853757; 329853757mRNA and protein:increased expression:gastrocnemius muscleRGD 
Spinal Cord Injuries  IEP 329853757mRNA and protein:increased expression:gastrocnemius muscleRGD 
Spinal Cord Injuries  ISORyr1 (Rattus norvegicus)329853757; 329853757protein:hyperoxidation and hypernitrosylation:gastrocnemius muscleRGD 
Spinal Cord Injuries  IDA 329853757protein:hyperoxidation and hypernitrosylation:gastrocnemius muscleRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nucleus  IDA 329853757MMO:0000679RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fkbp1b  (FKBP prolyl isomerase 1B)
Nox4  (NADPH oxidase 4)
Ryr1  (ryanodine receptor 1)

Genes (Mus musculus)
Fkbp1b  (FK506 binding protein 1b)
Nox4  (NADPH oxidase 4)
Ryr1  (ryanodine receptor 1, skeletal muscle)

Genes (Homo sapiens)
FKBP1B  (FKBP prolyl isomerase 1B)
NOX4  (NADPH oxidase 4)
RYR1  (ryanodine receptor 1)


Additional Information