PPARβ/δ 과발현은 PGC-1α ubiquitination의 감소를 통해 PGC-1α 단백질을 증가시킨다
PPARβ/δOverexpression Increase PGC-1αProtein through the Decreased PGC-1αUbiquitination in Mouse Skeletal Muscle
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PURPOSE: The aim of this study was to find mechanism with which PPARβ/δ control PGC-1αprotein stability in mouse skeletal muscle. METHODS: Tibialis anterior (TA) muscles of rat were dissected at 18h after 2 weeks swimming exercise. PPARβ/δ was over-expressed in mouse tibialis anterior (TA) muscle using electrical pulse-mediated gen transfer (electroporation; EPO) method. To evaluate, PGC-1α mRNA and protein, PPARβ/δ, ubiquitin and mitochondrial enzyme protein expression in mouse skeletal muscle, TA muscle were dissected at 2wk and 4wk after EPO. To evaluate binding between PGC-1α and ubiquitin, we conducted V5-PGC-1α Immunoprecipitation. RESULTS: PPARβ/δ and PGC-1α in swimming skeletal muscle for 2 weeks were increased 2.1 and 2.5 fold respectively than sedentary muscle. PGC-1α mRNA in PPARβ/δ over-expression skeletal muscle were not different at 2 wk and 4wk when compared to an empty vector (EV) treated group. Endogenous and exogenous PPARβ/δ in PPARβ/δ over-expression skeletal muscle were increased 2.5 and 3.8 fold respectively when compared to an EV treated group. We identified binding between PGC-1α and ubiquitin, and ubiquitin were decreased 60% in PPARβ/δ transfected C2C12 when compared to an EV treated group. PGC-1α were increased 3 fold in muscle that ubiquitin were decreased 60% when compared to an EV treated muscle and COXI and CYTO C were increased 2.27 and 1.75 fold respectively in muscle when compared to an EV treated muscle. CONCLUSIONS: PPARβ/δ overexpression increases PGC-1α protein through the decreased PGC-1α ubiquitination without the increased PGC-1α mRNA in mouse skeletal muscle.
Abstract
PURPOSE: The aim of this study was to find mechanism with which PPARβ/δ control PGC-1αprotein stability in mouse skeletal muscle. METHODS: Tibialis anterior (TA) muscles of rat were dissected at 18h after 2 weeks swimming exercise. PPARβ/δ was over-expressed in mouse tibialis anterior (TA) muscle using electrical pulse-mediated gen transfer (electroporation; EPO) method. To evaluate, PGC-1α mRNA and protein, PPARβ/δ, ubiquitin and mitochondrial enzyme protein expression in mouse skeletal muscle, TA muscle were dissected at 2wk and 4wk after EPO. To evaluate binding between PGC-1α and ubiquitin, we conducted V5-PGC-1α Immunoprecipitation. RESULTS: PPARβ/δ and PGC-1α in swimming skeletal muscle for 2 weeks were increased 2.1 and 2.5 fold respectively than sedentary muscle. PGC-1α mRNA in PPARβ/δ over-expression skeletal muscle were not different at 2 wk and 4wk when compared to an empty vector (EV) treated group. Endogenous and exogenous PPARβ/δ in PPARβ/δ over-expression skeletal muscle were increased 2.5 and 3.8 fold respectively when compared to an EV treated group. We identified binding between PGC-1α and ubiquitin, and ubiquitin were decreased 60% in PPARβ/δ transfected C2C12 when compared to an EV treated group. PGC-1α were increased 3 fold in muscle that ubiquitin were decreased 60% when compared to an EV treated muscle and COXI and CYTO C were increased 2.27 and 1.75 fold respectively in muscle when compared to an EV treated muscle. CONCLUSIONS: PPARβ/δ overexpression increases PGC-1α protein through the decreased PGC-1α ubiquitination without the increased PGC-1α mRNA in mouse skeletal muscle.
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