Sphingosine kinase modulates microvascular tone and myogenic responses through activation of RhoA/Rho kinase.
BACKGROUND
RhoA and Rho kinase are important modulators of microvascular tone.


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.
Bolz
Steffen-Sebastian
SS
Institute of Physiology, Ludwig Maximilians University, Schillerstrasse 44, 80336 Muenchen, Germany. bolz@lrz.uni-muenchen.de
Vogel
Lukas
L
Sollinger
Daniel
D
Derwand
Roland
R
Boer
Christa
C
Pitson
Stuart M
SM
Spiegel
Sarah
S
Pohl
Ulrich
U
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D046508:Culture Techniques; D004789:Enzyme Activation / Q000502:physiology; D005799:Genes, Dominant; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008833:Microcirculation / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014661:Vasoconstriction / Q000502:physiology; D014666:Vasomotor System / Q000502:physiology; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000099157:Sphingosine Kinase
D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000099157:Sphingosine Kinase