Abstract
Objective To study the effect of extracellular ATP on the FoxO3a pathway of myocytes of denervated gastrocnemius muscle. Methods Fifty-four female adult Wistar rats were randomly divided into three groups.In the two denervation groups,gastrocnemius muscle denervation was created by transecting the right sciatic nerve at the inferior border of piriformis.In the ATP treatment group,0.1mg/day ATP was injected into the right gastrocnemius muscle while the same amount of normal saline was injected into the left gastrocnemius for 4 weeks continuously.In the denervation control group,gastrocnemius muscle on both sides received normal saline injection.The third group of rats without any surgery and injections served as normal control.At 0,2,7,14 and 28 days postoperatively,rats from each denervation groups were sacrificed to harvest gastrocnemius muscle of both sides.Wet muscles were weighed and wet mumcle weight ratio (right/left) was calculated.The expression of p-FoxO3aS253,FoxO3a,MAFbx protein and mRNA were detected using Western Blot and quantitative RT-PCR respectively. Results The wet muscle weight ratio of the ATP treatment group was significantly higher than that of the denervation control group ( P ＜ 0.01).The expression FoxO3a mRNA and protein in the ATP treatment group was lower than these of the denervation control group.The difference,however,was not statistically significant (P＞0.05).The expression of MAFbx mRNA and protein showed the same trend as that of FoxO3a,but the difference was statistically significant ( P ＜ 0.05).p-FoxO3a protein expression remarkably increased in the ATP treatment group,the difference being statistically significant at different time points when compared with the control group ( P ＜ 0.05 ). Conclusion Extracellular ATP can potentially delay denervation muscle atrophy by inhibiting the expression of MAFbx protein via FoxO3a phosphorylation. Key words: Sciatic nerve; Muscular atrophy; Denervation; FoxO3a pathway; Extracellular ATP
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