Published online before print February 12, 2004, doi: 10.1161/01.RES.0000121101.32286.C8
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Submitted on September 22, 2003
Revised on January 23, 2004
Accepted on January 29, 2004
Restoration of Resting Sarcomere Length After Uniaxial Static Strain Is Regulated by Protein Kinase C
and Focal Adhesion Kinase
Haytham Mansour ;
From the Department of Physiology and Biophysics (H.M., P.P.d.T., B.R.), University of Illinois at Chicago, Chicago, Ill; the Cardiovascular Institute (A.M.S.), Loyola University Chicago Stritch School of Medicine, Maywood, Ill.
* To whom correspondence should be addressed. E-mail: russell{at}uic.edu.
Physiological or pathological stresses and strains produce longer or wider muscle cells, but resting sarcomere length remains constant. Our goal was to investigate the cellular mechanisms for controlling this optimal, resting sarcomere length. To do so, we cultured neonatal rat cardiomyocytes on microfabricated peg-and-groove, laminin-coated silicone surfaces and applied a uniaxial static strain of 10%. Sarcomere length was accurately measured by fast Fourier transform analysis of images before, within 5 minutes of, and 4 to 6 hours after imposition of the strain. Sarcomere length of aligned cardiomyocytes (1.94±0.07 µm) was lengthened acutely (2.06±0.06 µm), and recovered (1.95±0.07 µm) by 4 hours. Puromycin, an mRNA translational inhibitor, prevented recovery of resting sarcomere length by 4 hours, thus indicating a requirement for new protein synthesis in the recovery process. Furthermore, activation of protein kinase C
(PKC) was necessary for length recovery, as nonselective PKC inhibitors [staurosporine (5 µmol/L) and chelerythrine chloride (10 µmol/L)], and a replication-defective adenovirus (Adv) encoding a dominant-negative mutant of PKC prevented the restoration of sarcomere length. To assess the importance of focal adhesion complexes, cardiomyocytes were infected with an Adv encoding a dominant-negative inhibitor of focal adhesion kinase (FAK) (Adv-GFP-FRNK). Adv-GFP-FRNK also prevented resting sarcomere length recovery, whereas a control Adv encoding only GFP did not. In conclusion, using our novel culture system, we provide evidence indicating that the length remodeling process requires new protein synthesis, PKC and FAK.
Key words: microtopography • protein kinase C • signaling • mechanotransduction • remodeling
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