| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 275, Issue 18, 13802-13811, May 5, 2000
From The Wenner-Gren Institute, The Arrhenius Laboratories F3,
Stockholm University, SE-106 91 Stockholm, Sweden
To identify the signaling pathway that mediates
the adrenergic stimulation of the expression of the gene for vascular
endothelial growth factor (VEGF) during physiologically induced
angiogenesis, we examined mouse brown adipocytes in primary culture.
The endogenous adrenergic neurotransmitter norepinephrine (NE) induced
VEGF expression 3-fold, in a dose- and time-dependent
manner (EC50
Norepinephrine Induces Vascular Endothelial Growth Factor
Gene Expression in Brown Adipocytes through a
-Adrenoreceptor/cAMP/Protein Kinase A Pathway Involving Src but
Independently of Erk1/2*
,
90 nM). Also, the
hypoxia-mimicking agent cobalt, as well as serum and phorbol ester,
induced VEGF expression, but the effect of NE was additive to each of
these factors, implying that a separate signaling mechanism for the
NE-mediated induction was activated. The NE effect was abolished by
propranolol and mimicked by isoprenaline or BRL-37344 and was thus
mediated via 
-adrenoreceptors. The NE-induced VEGF expression was
fully cAMP mediated, an effect which was inhibited by H-89 and thus was
dependent on protein kinase A activity. Involvement of other adrenergic
signaling pathways (
1-adrenoreceptors, Ca2+,
protein kinase C, 2-adrenoreceptors, and pertussis
toxin-sensitive Gi-proteins) was excluded. The specific
inhibitor of Src tyrosine kinases, PP2, markedly reduced the
stimulation by NE, which demonstrates that a cAMP-dependent
Src-mediated pathway is positively connected to VEGF expression.
However, inhibition of Erk1/2 MAP kinases by PD98059 was without
effect. NE did not prolong VEGF mRNA half-life and its effect was
thus transcriptional, and was independent of protein synthesis. These
results demonstrate that adrenergic stimulation, through
-adrenoreceptor/cAMP/protein kinase A signaling, recruits a pathway
that branches off from the NE-activated Src-Erk1/2 cascade to enhance
transcription of the VEGF gene.
*
This work was supported by a grant from the Swedish Cancer
Foundation and by the Swedish Natural Science Research Council.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 46-8-164130;
Fax: 46-8-156756; E-mail: mf@zoofys.su.se.
§
On leave from the Institute of Cell Biophysics, Russian Academy of
Sciences, 142 292 Pushchino, Russia.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Xue, R. Cao, D. Nilsson, S. Chen, R. Westergren, E.-M. Hedlund, C. Martijn, L. Rondahl, P. Krauli, E. Walum, et al. FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue PNAS, July 22, 2008; 105(29): 10167 - 10172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Mastrangelo, A. Cassidy, F. Mulholland, W. Wang, and Y. Bao Serotonin Receptors, Novel Targets of Sulforaphane Identified by Proteomic Analysis in Caco-2 Cells Cancer Res., July 1, 2008; 68(13): 5487 - 5491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Hemmeryckx, R. van Bree, B. Van Hoef, L. Vercruysse, H. R. Lijnen, and J. Verhaeghe Adverse Adipose Phenotype and Hyperinsulinemia in Gravid Mice Deficient in Placental Growth Factor Endocrinology, May 1, 2008; 149(5): 2176 - 2183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Schwartz, J. George, J. Ben-Shoshan, G. Luboshits, I. Avni, H. Levkovitch-Verbin, H. Ziv, M. Rosner, and A. Barak Drug Modification of Angiogenesis in a Rat Cornea Model Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 250 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Nilsson, G. Armaiz-Pena, R. Takahashi, Y. G. Lin, J. Trevino, Y. Li, N. Jennings, J. Arevalo, S. K. Lutgendorf, G. E. Gallick, et al. Stress Hormones Regulate Interleukin-6 Expression by Human Ovarian Carcinoma Cells through a Src-dependent Mechanism J. Biol. Chem., October 12, 2007; 282(41): 29919 - 29926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hattori, S. Yamamoto, and N. Matsuda Sympathetic Control of VEGF Angiogenic Signaling: Dual Regulations by {alpha}2-Adrenoceptor Activation? Circ. Res., September 28, 2007; 101(7): 642 - 644. [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Oltmanns, H. Gehring, S. Rudolf, B. Schultes, C. Hackenberg, U. Schweiger, J. Born, H. L. Fehm, and A. Peters Acute hypoxia decreases plasma VEGF concentration in healthy humans Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E434 - E439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. F. Voelkel, R. W. Vandivier, and R. M. Tuder Vascular endothelial growth factor in the lung Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L209 - L221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Sood, R. Bhatty, A. A. Kamat, C. N. Landen, L. Han, P. H. Thaker, Y. Li, D. M. Gershenson, S. Lutgendorf, and S. W. Cole Stress Hormone-Mediated Invasion of Ovarian Cancer Cells Clin. Cancer Res., January 15, 2006; 12(2): 369 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Wiley, B. A. Berkowitz, and J. J. Steinle Superior Cervical Ganglionectomy Induces Changes in Growth Factor Expression in the Rat Retina Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 439 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Iaccarino, M. Ciccarelli, D. Sorriento, G. Galasso, A. Campanile, G. Santulli, E. Cipolletta, V. Cerullo, V. Cimini, G. G. Altobelli, et al. Ischemic Neoangiogenesis Enhanced by {beta}2-Adrenergic Receptor Overexpression: A Novel Role for the Endothelial Adrenergic System Circ. Res., November 25, 2005; 97(11): 1182 - 1189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. K.K. Wu, H. P.S. Wong, S. W. Luo, K. Chan, F. Y. Huang, M. K.C. Hui, E. K.Y. Lam, V. Y. Shin, Y. N. Ye, Y. H. Yang, et al. 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone from Cigarette Smoke Stimulates Colon Cancer Growth via {beta}-Adrenoceptors Cancer Res., June 15, 2005; 65(12): 5272 - 5277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Sommer, A. J. Hume, J. M. Ciak, J. J. VanNostrand, M. Friggens, and M. K. Walker Early Developmental 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure Decreases Chick Embryo Heart Chronotropic Response to Isoproterenol but Not to Agents Affecting Signals Downstream of the Beta-Adrenergic Receptor Toxicol. Sci., February 1, 2005; 83(2): 363 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Sounni, C. Roghi, V. Chabottaux, M. Janssen, C. Munaut, E. Maquoi, B. G. Galvez, C. Gilles, F. Frankenne, G. Murphy, et al. Up-regulation of Vascular Endothelial Growth Factor-A by Active Membrane-type 1 Matrix Metalloproteinase through Activation of Src-Tyrosine Kinases J. Biol. Chem., April 2, 2004; 279(14): 13564 - 13574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Dubrovska, S. Verlohren, F. C. Luft, and M. Gollasch Mechanisms of ADRF release from rat aortic adventitial adipose tissue Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1107 - H1113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. CANNON and J. NEDERGAARD Brown Adipose Tissue: Function and Physiological Significance Physiol Rev, January 1, 2004; 84(1): 277 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Lutgendorf, S. Cole, E. Costanzo, S. Bradley, J. Coffin, S. Jabbari, K. Rainwater, J. M. Ritchie, M. Yang, and A. K. Sood Stress-Related Mediators Stimulate Vascular Endothelial Growth Factor Secretion by Two Ovarian Cancer Cell Lines Clin. Cancer Res., October 1, 2003; 9(12): 4514 - 4521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Steinle, G. W. Booz, C. J. Meininger, J. N. E. Day, and H. J. Granger {beta}3-Adrenergic Receptors Regulate Retinal Endothelial Cell Migration and Proliferation J. Biol. Chem., May 30, 2003; 278(23): 20681 - 20686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. K. Anand, H.-J. Paust, K. Altenpohl, and A. K. Mukhopadhyay Regulation of Vascular Endothelial Growth Factor Production by Leydig Cells In Vitro: The Role of Protein Kinase A and Mitogen-Activated Protein Kinase Cascade Biol Reprod, May 1, 2003; 68(5): 1663 - 1673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Schmitt and P. J. S. Stork Galpha and Gbeta gamma Require Distinct Src-dependent Pathways to Activate Rap1 and Ras J. Biol. Chem., November 1, 2002; 277(45): 43024 - 43032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Chen, T. E. Solomon, E. P. Salazar, R. Kui, E. Rozengurt, and A. H. Soll Secretin regulates paracellular permeability in canine gastric monolayers by a Src kinase-dependent pathway Am J Physiol Gastrointest Liver Physiol, October 1, 2002; 283(4): G893 - G899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Mick, X. Wang, and K. McCormick White Adipocyte Vascular Endothelial Growth Factor: Regulation by Insulin Endocrinology, March 1, 2002; 143(3): 948 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Dantz, J. Bewersdorf, B. Fruehwald-Schultes, W. Kern, W. Jelkmann, J. Born, H. L. Fehm, and A. Peters Vascular Endothelial Growth Factor: A Novel Endocrine Defensive Response to Hypoglycemia J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 835 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.M. DALLABRIDA and M.A. RUPNICK Vascular Endothelium in Tissue Remodeling: Implications for Heart Failure Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 417 - 428. [Abstract] [PDF]
|
|
|
|
 |
|
 J. L. Segar, G. B. Dalshaug, K. A. Bedell, O. M. Smith, and T. D. Scholz Angiotensin II in cardiac pressure-overload hypertrophy in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2001; 281(6): R2037 - R2047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bousquet, V. Chesnokova, A. Kariagina, A. Ferrand, and S. Melmed cAMP Neuropeptide Agonists Induce Pituitary Suppressor of Cytokine Signaling-3: Novel Negative Feedback Mechanism for Corticotroph Cytokine Action Mol. Endocrinol., November 1, 2001; 15(11): 1880 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Pal, K. Datta, and D. Mukhopadhyay Central Role of p53 on Regulation of Vascular Permeability Factor/Vascular Endothelial Growth Factor (VPF/VEGF) Expression in Mammary Carcinoma Cancer Res., September 1, 2001; 61(18): 6952 - 6957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Purcell and T. J. Carew Modulation of Excitability in Aplysia Tail Sensory Neurons by Tyrosine Kinases J Neurophysiol, June 1, 2001; 85(6): 2398 - 2411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Lindquist, J. M. Fredriksson, S. Rehnmark, B. Cannon, and J. Nedergaard beta 3- and alpha 1-Adrenergic Erk1/2 Activation Is Src- but Not Gi-mediated in Brown Adipocytes J. Biol. Chem., July 21, 2000; 275(30): 22670 - 22677. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
