Contraction-mediated phosphorylation of AMPK is lower in skeletal muscle of adenylate kinase-deficient mice.
The activity of AMP-activated protein kinase (AMPK) increases during muscle contractions as a result of elevated AMP concentration. We tested whether activation of AMPK would be altered during contractions in adenylate kinase (AK) 1-deficient (AK1-/-) mice, because they have a reduced capacity to form AMP. The right gastrocnemius-soleus-plantaris muscle group was stimulated via the sciatic nerve at 2 Hz for 30 min in both wild-type (WT) and AK1-/- animals. Initial force production was not different between the two groups (129.2 +/- 3.3 g vs. 140.9 +/- 8.5 g for WT and AK1-/-, respectively); however, force production by AK1-/- mice was significantly greater over the 30-min stimulation period, and final tension was 85 +/- 4.5% of initial in WT and 102 +/- 3.2% of initial in AK1-/- mice. Western blot analysis showed that AMPK phosphorylation with contractions was clearly increased in WT muscles (4.0 +/- 1.1 above resting values), but did not change noticeably with AK deficiency (1.6 +/- 0.4 above WT resting values). However, increases in phosphorylation of acetyl CoA carboxylase were robust in both WT and AK1-/- muscles and not different between the two groups. These results suggest that reduced formation of AMP during contractions in skeletal muscle of AK1-/- mice results in reduced phosphorylation of AMPK. However, altered AMPK signaling was not apparent in the phosphorylation status of acetyl CoA carboxylase, a typical marker of AMPK activity.
Hancock
Chad R
CR
Medical Pharmacology and Physiology, College of Medicine, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
Janssen
Edwin
E
Terjung
Ronald L
RL
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000294:innervation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012584:Sciatic Nerve; D013997:Time Factors
D007527:Isoenzymes; D009097:Multienzyme Complexes; D000249:Adenosine Monophosphate; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000263:Adenylate Kinase; C110939:adenylate kinase 1; D000103:Acetyl-CoA Carboxylase