TY - JOUR
T1 - Na,K-ATPase activity in mouse muscle is regulated by AMPK and PGC-1a
AU - Ingwersen, Maria S
AU - Kristensen, Michael
AU - Pilegaard, Henriette
AU - Wojtaszewski, Jørgen
AU - Richter, Erik A.
AU - Juel, Carsten
N1 - CURIS 2011 5200 066
PY - 2011
Y1 - 2011
N2 - Na,K-ATPase activity, which is crucial for skeletal muscle function, undergoes acute and long-term regulation in response to muscle activity. The aim of the present study was to test the hypothesis that AMP kinase (AMPK) and the transcriptional coactivator PGC-1a are underlying factors in long-term regulation of Na,K-ATPase isoform (a,ß and PLM) abundance and Na(+) affinity. Repeated treatment of mice with the AMPK activator AICAR decreased total PLM protein content but increased PLM phosphorylation, whereas the number of a- and ß-subunits remained unchanged. The K (m) for Na(+) stimulation of Na,K-ATPase was reduced (higher affinity) after AICAR treatment. PLM abundance was increased in AMPK kinase-dead mice compared with control mice, but PLM phosphorylation and Na,K-ATPase Na(+) affinity remained unchanged. Na,K-ATPase activity and subunit distribution were also measured in mice with different degrees of PGC-1a expression. Protein abundances of a1 and a2 were reduced in PGC-1a +/- and -/- mice, and the ß(1)/ß(2) ratio was increased with PGC-1a overexpression (TG mice). PLM protein abundance was decreased in TG mice, but phosphorylation status was unchanged. Na,K-ATPase V (max) was decreased in PCG-1a TG and KO mice. Experimentally in vitro induced phosphorylation of PLM increased Na,K-ATPase Na(+) affinity, confirming that PLM phosphorylation is important for Na,K-ATPase function. In conclusion, both AMPK and PGC-1a regulate PLM abundance, AMPK regulates PLM phosphorylation and PGC-1a expression influences Na,K-ATPase a(1) and a(2) content and ß(1)/ß(2) isoform ratio. Phosphorylation of the Na,K-ATPase subunit PLM is an important regulatory mechanism.
AB - Na,K-ATPase activity, which is crucial for skeletal muscle function, undergoes acute and long-term regulation in response to muscle activity. The aim of the present study was to test the hypothesis that AMP kinase (AMPK) and the transcriptional coactivator PGC-1a are underlying factors in long-term regulation of Na,K-ATPase isoform (a,ß and PLM) abundance and Na(+) affinity. Repeated treatment of mice with the AMPK activator AICAR decreased total PLM protein content but increased PLM phosphorylation, whereas the number of a- and ß-subunits remained unchanged. The K (m) for Na(+) stimulation of Na,K-ATPase was reduced (higher affinity) after AICAR treatment. PLM abundance was increased in AMPK kinase-dead mice compared with control mice, but PLM phosphorylation and Na,K-ATPase Na(+) affinity remained unchanged. Na,K-ATPase activity and subunit distribution were also measured in mice with different degrees of PGC-1a expression. Protein abundances of a1 and a2 were reduced in PGC-1a +/- and -/- mice, and the ß(1)/ß(2) ratio was increased with PGC-1a overexpression (TG mice). PLM protein abundance was decreased in TG mice, but phosphorylation status was unchanged. Na,K-ATPase V (max) was decreased in PCG-1a TG and KO mice. Experimentally in vitro induced phosphorylation of PLM increased Na,K-ATPase Na(+) affinity, confirming that PLM phosphorylation is important for Na,K-ATPase function. In conclusion, both AMPK and PGC-1a regulate PLM abundance, AMPK regulates PLM phosphorylation and PGC-1a expression influences Na,K-ATPase a(1) and a(2) content and ß(1)/ß(2) isoform ratio. Phosphorylation of the Na,K-ATPase subunit PLM is an important regulatory mechanism.
U2 - 10.1007/s00232-011-9365-7
DO - 10.1007/s00232-011-9365-7
M3 - Journal article
C2 - 21687978
VL - 242
SP - 1
EP - 10
JO - Journal of Membrane Biology
JF - Journal of Membrane Biology
SN - 0022-2631
IS - 1
ER -