| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLE |
Division of Endocrinology, Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908
Address all correspondence and requests for reprints to: Jerry L. Nadler, Division of Endocrinology, Department of Internal Medicine, University of Virginia, P.O. Box 801405, Charlottesville, Virginia 22908. E-mail: jln2n{at}virginia.edu.
Evidence suggests that the 12-lipoxygenase (LO) pathway mediates angiotensin II (Ang II)-induced aldosterone synthesis in adrenal glomerulosa cells. To study the mechanisms of 12-LO pathway on aldosterone synthesis, the human adrenocortical cell line, H295R, was transiently transfected with a mouse leukocyte type of 12-LO. Overexpression of 12-LO stimulated aldosterone production 2.7-fold as well as the reporter gene activity of CYP11B2 gene-encoding human aldosterone synthase by 5-fold over that in mock-transfected cells. Ang II further enhanced aldosterone production, which could be blocked by a 12-LO inhibitor, baicalein, in mock cells and cells overexpressing 12-LO. Ang II stimulated cAMP response element-binding protein (CREB) phosphorylation in a dose- and time-dependent fashion in parent H295R cells. Overexpression of 12-LO increased phosphorylation of CREB/activating transcription factor (ATF)-1 1.5-fold over that in mock cells under basal conditions. Ang II led to a further 5.2- and 7.5-fold increase in mock cells and 12-LO cells, respectively. Overexpression of 12-LO induced p38 MAPK activation. The 12-LO product, 12-hydroxyeicosatetraenoic acid, increased phosphorylation of CREB/ATF-1 3.6-fold and phosphorylation of p38 MAPK 8-fold over basal. The p38 MAPK inhibitor SB203580 inhibited Ang II- and 12-LO pathway-induced phosphorylated CREB/ATF-1, suggesting a role of p38 MAPK in Ang II and 12-LO pathway signaling. These results suggest that 12-LO stimulation leads to aldosterone production in H295R cells in part through activation of CREB/ATF-1 and p38 MAPK pathway.
This article has been cited by other articles:
 |
|
 |
|
  E. F Nogueira, C. A Vargas, M. Otis, N. Gallo-Payet, W. B Bollag, and W. E Rainey Angiotensin-II acute regulation of rapid response genes in human, bovine, and rat adrenocortical cells J. Mol. Endocrinol., December 1, 2007; 39(6): 365 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Casal, S. Ryser, A. M. Capponi, and C. F. Wang-Buholzer Angiotensin II-Induced Mitogen-Activated Protein Kinase Phosphatase-1 Expression in Bovine Adrenal Glomerulosa Cells: Implications in Mineralocorticoid Biosynthesis Endocrinology, November 1, 2007; 148(11): 5573 - 5581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Inagaki, F. Otsuka, J. Suzuki, Y. Kano, M. Takeda, T. Miyoshi, H. Otani, Y. Mimura, T. Ogura, and H. Makino Involvement of Bone Morphogenetic Protein-6 in Differential Regulation of Aldosterone Production by Angiotensin II and Potassium in Human Adrenocortical Cells Endocrinology, June 1, 2006; 147(6): 2681 - 2689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gambaryan, E. Butt, P. Tas, A. Smolenski, B. Allolio, and U. Walter Regulation of aldosterone production from zona glomerulosa cells by ANG II and cAMP: evidence for PKA-independent activation of CaMK by cAMP Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E423 - E433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-G. LeHoux and A. Lefebvre Novel protein kinase C-epsilon inhibits human CYP11B2 gene expression through ERK1/2 signalling pathway and JunB J. Mol. Endocrinol., February 1, 2006; 36(1): 51 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Xu, B. Jiang, K. A. Maitland, H. Bayat, J. Gu, J. L. Nadler, S. Corda, G. Lavielle, T. J. Verbeuren, A. Zuccollo, et al. The Thromboxane Receptor Antagonist S18886 Attenuates Renal Oxidant Stress and Proteinuria in Diabetic Apolipoprotein E-Deficient Mice Diabetes, January 1, 2006; 55(1): 110 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Pei, J. Gu, P.-R. Thimmalapura, A. Mison, and J. L. Nadler Activation of the 12-lipoxygenase and signal transducer and activator of transcription pathway during neointima formation in a model of the metabolic syndrome Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E92 - E102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Enyeart, S. J. Danthi, and J. J. Enyeart TREK-1 K+ channels couple angiotensin II receptors to membrane depolarization and aldosterone secretion in bovine adrenal glomerulosa cells Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1154 - E1165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. SPAT and L. HUNYADY Control of Aldosterone Secretion: A Model for Convergence in Cellular Signaling Pathways Physiol Rev, April 1, 2004; 84(2): 489 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Tsybouleva, L. Zhang, S. Chen, R. Patel, S. Lutucuta, S. Nemoto, G. DeFreitas, M. Entman, B. A. Carabello, R. Roberts, et al. Aldosterone, Through Novel Signaling Proteins, Is a Fundamental Molecular Bridge Between the Genetic Defect and the Cardiac Phenotype of Hypertrophic Cardiomyopathy Circulation, March 16, 2004; 109(10): 1284 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Suzuki, F. Otsuka, K. Inagaki, M. Takeda, T. Ogura, and H. Makino Novel Action of Activin and Bone Morphogenetic Protein in Regulating Aldosterone Production by Human Adrenocortical Cells Endocrinology, February 1, 2004; 145(2): 639 - 649. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
