Effects Of Exercise On The Association Of HDAC5 With MEF2 In Skeletal Muscle Of Different Genotypic Mice Of AMPK

Histone deacetylase 5(HDAC5) is a member of classⅡa family and is abundant in skeletal muscle of mammalian. As a corepressor of transcription factor MEF2, HDAC5 could repress MEF2-dependent gene transcription in promoter region by means of hi stone acetylation modification. Following AICAR treatment in vitro,AMPK could phosphorylate HDAC5 and induce its nuclear export, which will relieve repression of MEF2-dependent transcription. Experiment in vivo also found that the association of HDAC5 with MEF2 was reduced after exercise, accompany with nucleus export of HDAC5. However, there have been no experiments in vivo revealing the relationship among AMPK, HDAC5 and MEF2 up to now.Objective:As AMPK could be activated during exercise, the aim of this study is to explore the role of AMPKα2 in regulating HDAC5 and MEF2 interaction during exercise by mesuring several skeletal muscle indexes about HDAC5 and MEF2, after four weeks'endurance training of three types of AMPKα2 genetic mice.Methods:Two months old of C57BL/6J wild-type mice(n=20),α2-AMPK over-expression mice (n=20) andα2-AMPK whole-body knockout mice(n=2O) were randomly subdivided into control groups and exercise groups. After four weeks'treadmill running(12m/min, lh/day),the association of HDAC5 with MEF2 in nucleus of quadriceps femoris muscle was measured by co-immunoprecipitation, nucleus HDAC5 protein and totle HDAC5 protein expressions were measured by western blot.Results:After four weeks'endurance training, (1) association of HDAC5 with MEF2 in skeletal muscle of three genetic types of mice were all significantly lower than control groups, while there were no significant differences among three exercise groups. (2)Nucleus HDAC5 protein expressions in skeletal muscle of three genetic types of mice were all significantly lower than control groups, and there was significant difference between group TO and TW. (3)Totle HDAC5 protein expressions in skeletal muscle of three genetic types of mice had no changes comparing to control groups.Conclutions:(1)Four weeks'endurance training induced reduction of association of HDAC5 with MEF2 and HDAC5 nucleus export in skeletal muscle of three genetic types of mice;(2)Comparing to WT mice, nucleus HDAC5 expression in skeletal muscle of OE mice significantly reduced after four weeks'endurance training;(3)There were no significant differences between WT mice and KO mice in the amount that HDAC5 accossiated with MEF2, nucleus and totle HDAC5 expressions of skeletal muscle after four weeks'endurance training.There may be other pathways which regulatead association of HDAC5 with MEF2 and nucleus HDAC5 expression besides AMPK a 2-dependent pathway.