Stretch-induced ERK2 phosphorylation requires PLA2 activity in skeletal myotubes.
Mechanical stretch rapidly activates multiple signaling cascades, including phospholipases and kinases, to stimulate protein synthesis and growth. The purpose of this study was to determine whether PLA2 activation contributes to stretch-induced phosphorylation of ERK2 in skeletal muscle myotubes. Myotubes derived from neonatal C57 mice were cultured on silicone membranes and subjected to brief cyclic stretch. Inhibition of PLA2 prevented ERK2 phosphorylation, while inhibition of prostaglandin or leukotriene synthesis did not. ERK2 phosphorylation was also blocked by genistein and PD98059, implicating the canonical raf-MEK-ERK cassette. It appears that PLA2, but not further metabolism of arachidonic acid, is required for stretch-induced activation of ERK2. Exposure to exogenous arachidonic acid had no effect on ERK2 phosphorylation, but exposure to lysophosphatidylcholine, the other metabolite of PLA2, caused a dose-dependent increase in ERK2 phosphorylation. These results suggest that stretch-induced activation of ERK2 may result from an interaction between PLA2 derived lysophosphatidylcholine and membrane receptors.
Burkholder
Thomas J
TJ
School of Applied Physiology and Interdisciplinary Bioengineering Program, Georgia Institute of Technology, 281 Ferst Drive, Atlanta, GA 30332-0356, USA. thomas.burkholder@hps.gatech.edu
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000502:physiology*; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013314:Stress, Mechanical
D005419:Flavonoids; D008244:Lysophosphatidylcholines; D064801:Phospholipase A2 Inhibitors; D047428:Protein Kinase Inhibitors; D019833:Genistein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D054467:Phospholipases A2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one