Effect of Inhibiting p38 on HuR Involving in β-AChR Post-transcriptional Mechanisms in Denervated Skeletal Muscle
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Previous studies reported that RNA-binding protein human antigen R (HuR) mediates changes in the stability of AChR β-subunit mRNA after skeletal muscle denervation; also, p38 pathway regulated the stability of AChR β-subunit mRNA in C2C12 myotubes. However, the relationship between HuR and p38 in regulating the stability of AChR β-subunit mRNA have not been clarified. In this study, we wanted to examine the effect of inhibiting p38 on HuR in denervated skeletal muscle. Denervation model was built and 10% DMSO or SB203580 were administered respectively follow denervation. Tibialis muscles were collected in 10% DMSO-administered contralateral (undenervated) leg, 10% DMSO-administered denervated leg, SB203580-administered contralateral (undenervated) leg, and SB203580-administered denervated leg, respectively. P38 protein, β-AChR mRNA and protein, HuR protein, β-AChR mRNA stability, and HuR binding with AChR β-subunit mRNAs were measured. Results demonstrated that the administration of SB203580 can inhibit the increase of β-AChR protein expression and mRNA expression and stability, and RNA-binding protein human antigen R (HuR) expression, in cytoplasmic and nuclear fractions in skeletal muscle cells following denervation. Importantly, we observed that SB203580 also inhibited the increased level of binding activity between HuR and AChR β-subunit mRNAs following denervation. Collectively, these results suggested that inhibition of p38 can post-transcriptionally inhibit β-AChR upregulation via HuR in denervated skeletal muscle.
KeywordsAcetylcholine receptors p38 inhibitor Human antigen R Denervation Post-transcriptional mechanisms
HW and S-tL designed the study. HW carried out the study and drafted the manuscript. XZ collected important background information and performed the statistical analysis. HW, XZ, and YW carried out the molecular biology experiments. L-HC carried out literature, data acquisition, and manuscript editing. All authors reviewed the manuscript.
The present study was funded by the National Natural Science Foundation of China (No. 81772121).
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Conflict of interest
The authors declare that they have no conflicts of interest.
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