RGD Reference Report - Phosphodiesterase 4B knockout prevents skeletal muscle atrophy in rats with burn injury. - Rat Genome Database

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Phosphodiesterase 4B knockout prevents skeletal muscle atrophy in rats with burn injury.

Authors: Balasubramaniam, Ambikaipakan  Sheriff, Sulaiman  Friend, Lou Ann  James, J Howard 
Citation: Balasubramaniam A, etal., Am J Physiol Regul Integr Comp Physiol. 2018 Aug 1;315(2):R429-R433. doi: 10.1152/ajpregu.00042.2018. Epub 2018 Apr 25.
RGD ID: 13782127
Pubmed: PMID:29693432   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpregu.00042.2018   (Journal Full-text)

The phosphodiesterase 4 (PDE4)-cAMP pathway plays a predominant role in mediating skeletal muscle proteolysis in burn injury. The present investigations to determine the PDE4 isoform(s) involved in this action revealed that burn injury increased the expression of rat skeletal muscle PDE4B mRNA by sixfold but had little or no effect on expression of other PDE4 isoforms. These observations led us to study the effects of burn in PDE4B knockout (KO) rats. As reported by us previously, burn injury significantly increased extensor digitorum longus (EDL) muscle total and myofibrillar proteolysis in wild-type (WT) rats, but there were no significant effects on either total or myofibrillar protein breakdown in EDL muscle of PDE4B KO rats with burn injury. Moreover, burn injury increased PDE4 activity in the skeletal muscle of WT rats, but this was reduced by >80% in PDE4B KO rats. Also, burn injury decreased skeletal muscle cAMP concentration in WT rats but had no significant effects in the muscles of PDE4B KO rats. Incubation of the EDL muscle of burn-PDE4B KO rats with an inhibitor of the exchange factor directly activated by cAMP, but not with a protein kinase A inhibitor, eliminated the protective effects of PDE4B KO on EDL muscle proteolysis and increased muscle proteolysis to the same extent as in the EDL of burn-WT rats. These novel findings confirm a major role for PDE4B in skeletal muscle proteolysis in burn injury and suggest that an innovative therapy based on PDE4B-selective inhibitors could be developed to treat skeletal muscle cachexia in burn injury without the fear of causing emesis, which is associated with PDE4D inhibition.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Burns  ISOPde4b (Rattus norvegicus)13782127; 13782127mRNA:increased expression:extensor digitorum longus muscleRGD 
Burns  IEP 13782127mRNA:increased expression:extensor digitorum longus muscleRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pde4b  (phosphodiesterase 4B)

Genes (Mus musculus)
Pde4b  (phosphodiesterase 4B, cAMP specific)

Genes (Homo sapiens)
PDE4B  (phosphodiesterase 4B)

Objects referenced in this article
Gene Pde4bem1Sage phosphodiesterase 4B; ZFN induced mutant1, Sage Rattus norvegicus
Strain SD-Pde4bem1Sage null Rattus norvegicus

Additional Information