Journal of Applied Physiology Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 91: 1574-1581, 2001;
8750-7587/01 $5.00
This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (55)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Go, Y.-M.
Right arrow Articles by Jo, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Go, Y.-M.
Right arrow Articles by Jo, H.
Vol. 91, Issue 4, 1574-1581, October 2001

Protein kinase B/Akt activates c-Jun NH2-terminal kinase by increasing NO production in response to shear stress

Young-Mi Go1,*, Yong Chool Boo1,*, Heonyong Park1, Matthew C. Maland1, Rakesh Patel2, Kirkwood A. Pritchard Jr.3, Yasushi Fujio4, Kenneth Walsh4, Victor Darley-Usmar2, and Hanjoong Jo1

1 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30322; 2 Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294; 3 Division of Pediatric Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226; and 4 Division of Cardiovascular Research, St. Elizabeth's Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02135

Laminar shear stress activates c-Jun NH2-terminal kinase (JNK) by the mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase (PI3K). Because protein kinase B (Akt), a downstream effector of PI3K, has been shown to phosphorylate and activate endothelial NO synthase, we hypothesized that Akt regulates shear-dependent activation of JNK by stimulating NO production. Here, we examined the role of Akt in shear-dependent NO production and JNK activation by expressing a dominant negative Akt mutant (AktAA) and a constitutively active mutant (AktMyr) in bovine aortic endothelial cells (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin) prevented shear-dependent stimulation of Akt and NO production. Transient expression of AktAA in BAEC by using a recombinant adenoviral construct inhibited the shear-dependent stimulation of NO production and JNK activation. However, transient expression of AktMyr by using a recombinant adenoviral construct did not induce JNK activation. This is consistent with our previous finding that NO is required, but not sufficient on its own, to activate JNK in response to shear stress. These results and our previous findings strongly suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO synthase, leading to production of NO, which (along with O<UP><SUB>2</SUB><SUP>−</SUP></UP>, which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK by shear stress is likely to play a critical role in its antiatherogenic effects.

endothelial cells; mitogen-activated protein kinase; atherosclerosis; endothelial nitric oxide synthase; mechanosensing

* Y.-M. Go and Y. C. Boo contributed equally to this work.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
L. Ai, M. Rouhanizadeh, J. C. Wu, W. Takabe, H. Yu, M. Alavi, R. Li, Y. Chu, J. Miller, D. D. Heistad, et al.
Shear stress influences spatial variations in vascular Mn-SOD expression: implication for LDL nitration
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1576 - C1585.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. L. Mowbray, D.-H. Kang, S. G. Rhee, S. W. Kang, and H. Jo
Laminar Shear Stress Up-regulates Peroxiredoxins (PRX) in Endothelial Cells: PRX 1 AS A MECHANOSENSITIVE ANTIOXIDANT
J. Biol. Chem., January 18, 2008; 283(3): 1622 - 1627.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
K. Chang, D. Weiss, J. Suo, J. D. Vega, D. Giddens, W. R. Taylor, and H. Jo
Bone Morphogenic Protein Antagonists Are Coexpressed With Bone Morphogenic Protein 4 in Endothelial Cells Exposed to Unstable Flow In Vitro in Mouse Aortas and in Human Coronary Arteries: Role of Bone Morphogenic Protein Antagonists in Inflammation and Atherosclerosis
Circulation, September 11, 2007; 116(11): 1258 - 1266.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. Miyahara, K. Hamanaka, D. S. Weber, D. A. Drake, M. Anghelescu, and J. C. Parker
Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungs
Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L11 - L21.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
F. A. Kudo, A. Muto, S. P. Maloney, J. M. Pimiento, S. Bergaya, T. N. Fitzgerald, T. S. Westvik, J. C. Frattini, C. K. Breuer, C. H. Cha, et al.
Venous Identity Is Lost but Arterial Identity Is Not Gained During Vein Graft Adaptation
Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1562 - 1571.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
Y. S. Chatzizisis, A. U. Coskun, M. Jonas, E. R. Edelman, C. L. Feldman, and P. H. Stone
Role of Endothelial Shear Stress in the Natural History of Coronary Atherosclerosis and Vascular Remodeling: Molecular, Cellular, and Vascular Behavior
J. Am. Coll. Cardiol., June 26, 2007; 49(25): 2379 - 2393.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Wang, J. Chang, K.-D. Chen, S. Li, J. Y.-S. Li, C. Wu, and S. Chien
Selective adapter recruitment and differential signaling networks by VEGF vs. shear stress
PNAS, May 22, 2007; 104(21): 8875 - 8879.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. O. Platt, R. F. Ankeny, G.-P. Shi, D. Weiss, J. D. Vega, W. R. Taylor, and H. Jo
Expression of cathepsin K is regulated by shear stress in cultured endothelial cells and is increased in endothelium in human atherosclerosis
Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1479 - H1486.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Gautam, Y. Shen, T. L. Thirkill, G. C. Douglas, and A. I. Barakat
Flow-activated Chloride Channels in Vascular Endothelium: SHEAR STRESS SENSITIVITY, DESENSITIZATION DYNAMICS, AND PHYSIOLOGICAL IMPLICATIONS
J. Biol. Chem., December 1, 2006; 281(48): 36492 - 36500.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
X.-P. Zhang and T. H. Hintze
cAMP signal transduction induces eNOS activation by promoting PKB phosphorylation
Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2376 - H2384.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C.-W. Yang, W.-L. Chen, P.-L. Wu, H.-Y. Tseng, and S.-J. Lee
Anti-Inflammatory Mechanisms of Phenanthroindolizidine Alkaloids
Mol. Pharmacol., March 1, 2006; 69(3): 749 - 758.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. Li, K.-R. Chiou, A. Bugayenko, K. Irani, and D. A. Kass
Reduced Wall Compliance Suppresses Akt-Dependent Apoptosis Protection Stimulated by Pulse Perfusion
Circ. Res., September 16, 2005; 97(6): 587 - 595.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
N. Mehebik, A.-M. Jaubert, D. Sabourault, Y. Giudicelli, and C. Ribiere
Leptin-induced nitric oxide production in white adipocytes is mediated through PKA and MAP kinase activation
Am J Physiol Cell Physiol, August 1, 2005; 289(2): C379 - C387.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. C. Krepinsky, Y. Li, Y. Chang, L. Liu, F. Peng, D. Wu, D. Tang, J. Scholey, and A. J. Ingram
Akt Mediates Mechanical Strain-Induced Collagen Production by Mesangial Cells
J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1661 - 1672.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z.-G. Jin, C. Wong, J. Wu, and B. C. Berk
Flow Shear Stress Stimulates Gab1 Tyrosine Phosphorylation to Mediate Protein Kinase B and Endothelial Nitric-oxide Synthase Activation in Endothelial Cells
J. Biol. Chem., April 1, 2005; 280(13): 12305 - 12309.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
C. K. Roberts, R. J. Barnard, R. K. Sindhu, M. Jurczak, A. Ehdaie, and N. D. Vaziri
A high-fat, refined-carbohydrate diet induces endothelial dysfunction and oxidant/antioxidant imbalance and depresses NOS protein expression
J Appl Physiol, January 1, 2005; 98(1): 203 - 210.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Czarny and J. E. Schnitzer
Neutral sphingomyelinase inhibitor scyphostatin prevents and ceramide mimics mechanotransduction in vascular endothelium
Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1344 - H1352.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. Kotani, T. Kotani, Z. Li, R. Silbajoris, C.A. Piantadosi, and Y-C.T. Huang
Reduced inspiratory flow attenuates IL-8 release and MAPK activation of lung overstretch
Eur. Respir. J., August 1, 2004; 24(2): 238 - 246.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. G. Arndt, N. Suzuki, N. J. Avdi, K. C. Malcolm, and G. S. Worthen
Lipopolysaccharide-induced c-Jun NH2-terminal Kinase Activation in Human Neutrophils: ROLE OF PHOSPHATIDYLINOSITOL 3-KINASE AND Syk-MEDIATED PATHWAYS
J. Biol. Chem., March 19, 2004; 279(12): 10883 - 10891.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
U. Uhlig, H. Fehrenbach, R. A. Lachmann, T. Goldmann, B. Lachmann, E. Vollmer, and S. Uhlig
Phosphoinositide 3-OH Kinase Inhibition Prevents Ventilation-induced Lung Cell Activation
Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 201 - 208.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Kaplan-Albuquerque, C. Garat, C. Desseva, P. L. Jones, and R. A. Nemenoff
Platelet-derived Growth Factor-BB-mediated Activation of Akt Suppresses Smooth Muscle-specific Gene Expression through Inhibition of Mitogen-activated Protein Kinase and Redistribution of Serum Response Factor
J. Biol. Chem., October 10, 2003; 278(41): 39830 - 39838.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. van Haperen, C. Cheng, B. M. E. Mees, E. van Deel, M. de Waard, L. C.A. van Damme, T. van Gent, T. van Aken, R. Krams, D. J. Duncker, et al.
Functional Expression of Endothelial Nitric Oxide Synthase Fused to Green Fluorescent Protein in Transgenic Mice
Am. J. Pathol., October 1, 2003; 163(4): 1677 - 1686.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Rocic, P. Seshiah, and K. K. Griendling
Reactive Oxygen Species Sensitivity of Angiotensin II-dependent Translation Initiation in Vascular Smooth Muscle Cells
J. Biol. Chem., September 19, 2003; 278(38): 36973 - 36979.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
Y. C. Boo and H. Jo
Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases
Am J Physiol Cell Physiol, September 1, 2003; 285(3): C499 - C508.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
Z.-G. Jin, H. Ueba, T. Tanimoto, A. O. Lungu, M. D. Frame, and B. C. Berk
Ligand-Independent Activation of Vascular Endothelial Growth Factor Receptor 2 by Fluid Shear Stress Regulates Activation of Endothelial Nitric Oxide Synthase
Circ. Res., August 22, 2003; 93(4): 354 - 363.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. P. Sorescu, M. Sykes, D. Weiss, M. O. Platt, A. Saha, J. Hwang, N. Boyd, Y. C. Boo, J. D. Vega, W. R. Taylor, et al.
Bone Morphogenic Protein 4 Produced in Endothelial Cells by Oscillatory Shear Stress Stimulates an Inflammatory Response
J. Biol. Chem., August 15, 2003; 278(33): 31128 - 31135.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
N. L. Boyd, H. Park, H. Yi, Y. C. Boo, G. P. Sorescu, M. Sykes, and H. Jo
Chronic shear induces caveolae formation and alters ERK and Akt responses in endothelial cells
Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1113 - H1122.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
B. Illi, S. Nanni, A. Scopece, A. Farsetti, P. Biglioli, M. C. Capogrossi, and C. Gaetano
Shear Stress-Mediated Chromatin Remodeling Provides Molecular Basis for Flow-Dependent Regulation of Gene Expression
Circ. Res., July 25, 2003; 93(2): 155 - 161.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
B. Wojciak-Stothard and A. J. Ridley
Shear stress-induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases
J. Cell Biol., April 28, 2003; 161(2): 429 - 439.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Wedgwood, C. J. Mitchell, J. R. Fineman, and S. M. Black
Developmental differences in the shear stress-induced expression of endothelial NO synthase: changing role of AP-1
Am J Physiol Lung Cell Mol Physiol, April 1, 2003; 284(4): L650 - L662.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. C. Boo, J. Hwang, M. Sykes, B. J. Michell, B. E. Kemp, H. Lum, and H. Jo
Shear stress stimulates phosphorylation of eNOS at Ser635 by a protein kinase A-dependent mechanism
Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1819 - H1828.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. C. Boo, G. Sorescu, N. Boyd, I. Shiojima, K. Walsh, J. Du, and H. Jo
Shear Stress Stimulates Phosphorylation of Endothelial Nitric-oxide Synthase at Ser1179 by Akt-independent Mechanisms. ROLE OF PROTEIN KINASE A
J. Biol. Chem., January 25, 2002; 277(5): 3388 - 3396.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online