Altered PKC expression and phosphorylation in response to the nature, direction, and magnitude of mechanical stretch.
Protein kinase C (PKC) isozymes have been shown to play a role in mechanotransduction in a variety of cell types. We sought to identify the PKC isozymes involved in transducing mechanical (cyclic vs. static), direction and intensity of stretch by examining changes in protein expression and phosphorylation. We used a 3-dimensional culture system with aligned neonatal rat cardiac myocytes on silastic membranes. Myocytes were subjected to either cyclic stretch at 5 cycles/min or static stretch for a period of 24 h at intensities of 0%, 2.5%, 5%, or 10% of full membrane length. Stretch was applied in perpendicular or parallel directions to myocyte alignment. PKC delta was most sensitive to stretch applied perpendicular to myocyte alignment regardless of the nature of stretch, while phospho PKC delta T505 increased in response to static-perpendicular stretch. PKC epsilon expression was altered by cyclic stretch but not static stretch, while phospho PKC epsilon S719 remained unchanged. PKC alpha expression was not altered by stretch; however, phospho PKC alpha S657 increased in a dose-dependent manner following cyclic-perpendicular stretch. Our results indicate that changes in PKC expression and phosphorylation state may be a mechanism for cardiac myocytes to discriminate between the nature, direction, and intensity of mechanical stretch.
Bullard
Tara A
TA
Department of Cell and Developmental Biology and Anatomy, University of South Carolina, School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209, USA. tara_bullard@urmc.rochester.edu
Hastings
Joshua L
JL
Davis
Jeffrey M
JM
Borg
Thomas K
TK
Price
Robert L
RL
D000818:Animals; D002478:Cells, Cultured; D007527:Isoenzymes / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000201:enzymology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical
D007527:Isoenzymes; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon