BACKGROUND: RhoA and Rho kinase are important modulators of microvascular tone. METHODS AND RESULTS: We tested whether sphingosine kinase (Sphk1) that generates the endogenous sphingolipid mediator sphingosine-1-phosphate (S1P) is part of a signaling cascade to activate the RhoA/Rho kinase pathway. Using a new transfection model, we report that resting tone and myogenic responses of isolated resistance arteries increased with forced expression of Sphk1 in smooth muscle cells of these arteries. Overexpression of a dominant negative Sphk1 mutant or coexpression of dominant negative mutants of RhoA or Rho kinase together with Sphk1 completely inhibited development of tone and myogenic responses. CONCLUSIONS: The tone-increasing effects of a Sphk1 overexpression suggest that Sphk1 may play an important role in the control of peripheral resistance.
BACKGROUND:RhoA and Rho kinase are important modulators of microvascular tone. METHODS AND RESULTS: We tested whether sphingosine kinase (Sphk1) that generates the endogenous sphingolipid mediator sphingosine-1-phosphate (S1P) is part of a signaling cascade to activate the RhoA/Rho kinase pathway. Using a new transfection model, we report that resting tone and myogenic responses of isolated resistance arteries increased with forced expression of Sphk1 in smooth muscle cells of these arteries. Overexpression of a dominant negative Sphk1 mutant or coexpression of dominant negative mutants of RhoA or Rho kinase together with Sphk1 completely inhibited development of tone and myogenic responses. CONCLUSIONS: The tone-increasing effects of a Sphk1 overexpression suggest that Sphk1 may play an important role in the control of peripheral resistance.
Authors: Parker C Wilson; Wayne R Fitzgibbon; Sara M Garrett; Ayad A Jaffa; Louis M Luttrell; Michael W Brands; Hesham M El-Shewy Journal: Mol Endocrinol Date: 2015-04-14
Authors: Regina Alemany; Chris J van Koppen; Kerstin Danneberg; Michael Ter Braak; Dagmar Meyer Zu Heringdorf Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2007-01-23 Impact factor: 3.000
Authors: Bernhard Friedrich Peter; Darcy Lidington; Aki Harada; Hanno Jörn Bolz; Lukas Vogel; Scott Heximer; Sarah Spiegel; Ulrich Pohl; Steffen-Sebastian Bolz Journal: Circ Res Date: 2008-06-26 Impact factor: 17.367