Third-party-funded project
Title:
Regulation of aldosterone synthesis and the 'steroidogenic acute regulator protein' (StAR) by cGMP-dependent protein kinase type II.
Project management at the University of Würzburg:
Participating scientists:
Abstract:
Atrial Natriuretic Peptides (ANP) and nitric oxide (NO) are potent inhibitors of agonist-induced aldosterone synthesis in zona glomerulosa cells of adrenal glands. ANP and NO achieve many of their intracellular effects via the messenger molecule cGMP. In preliminary experiments we established that the cyclic GMP-dependent protein kinase type II (cGK-II) is expressed in aldosterone-producing cells. Therefore, the goal of this DFG-supported study is to elucidate the molecular mechanisms of cyclic GMP-dependent protein kinase type II (cGK-II) in regulation of aldosterone synthesis and release from zona glomerulosa cells. The information deriving from our project will be of potential use for a) developing new drug strategies for the inhibition of the renin-angiotensin-aldosterone-system (RAAS) and b) for a better understanding of adrenal tumorigenesis especially with regard to aldosterone-producing tumors.
Key words:
renin
aldosterone
protein kinases
cGMP
nitric oxide
ANP
Projekt period:
from 12.2001 to 12.2003
Funding institution:
DFG ,Granting date: 06.12.2001
Publications:
- Pierkes M, Gambaryan S, Boknik P, Lohmann SM, Schmitz W, Potthast R, Holtwick R, Kuhn M.
(2002). Increased effects of C-type natriuretic peptide on cardiac ventricular contractility and relaxation in guanylyl cyclase A- deficient mice. Cardiovascular Research. 2002;53:852-861, (scientific article)
- Gambaryan S, Palmetshofer A, Glazova M, Smolenski A, Kristjansson GI, Zimmer M, Lohmann SM.
(2002). Inhibition of cGMP-dependent protein kinase II by its own splice isoform. Biochemical and Biophysical Research Communications. 2002;293:1438-1444, (scientific article)
- Dohna M., Reincke M., Mincheva A., Allolio B., Solinas-Toldo S., Lichter P..
(2000). Dohna M., Reincke M., Mincheva A., Allolio B., Solinas-Toldo S., Lichter P. Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications. . Genes Chromosomes Cancer. 2000; 28: 145-152, (scientific article)
- Zenkert S, Schubert B, Fassnacht M, Beuschlein F, Allolio B, Reincke M.
(2000). Steroidogenic acute regulatory protein mRNA expression in adrenal tumours. Eur J Endocrinol. 2000; 142: 294-299, (scientific article)
- Fassnacht M, Hahner S, Beuschlein F, Klinik A, Reincke M, Allolio B.
(2000). New mechanisms of adrenostatic compounds in a human adrenocortical cancer cell line. Eur J Clin Invest. 2000; 30: 76-82, (scientific article)
- Fischer TA, Palmetshofer A, Gambaryan S, Butt E, Jassoy C, Walter U, Sopper S, Lohmann SM.
(2000). Activation of cGMP-dependent protein kinase Ib inhibits IL-2 release and proliferation of T cell receptor-stimulated human peripheral T cells. J. Biol. Chem. 2000; 276: 5967 ? 5974, (scientific article)
- Hoenderop JG, Vaandrager AB, Dijkink L, Smolenski A, Gambaryan S, Lohmann SM, de Jonge HR, Willems PH, Bindels RJ.
(1999). Atrial natriuretic peptide-stimulated Ca2+ reabsorption in rabbit kidney requires membrane-targeted, cGMP-dependent protein kinase type II. Proc Natl Acad Sci U S A. 1999; 96:6084-6089, (scientific article)
- Eigenthaler M, Lohmann SM, Walter U, Pilz RB.
(1999). Signal transduction by cGMP dependent protein kinases and their emerging roles in the regulation of cell adhesion and gene expression. . Reviews of Physiology, Biochemistry, and Pharmacology 1999; 135: 173 ? 209, (scientific article)
- Gambaryan S, Wagner C, Smolenski A, Walter U, Poller W, Haase W, Kurtz A, Lohmann SM.
(1998). cAMP-stimulated renin release from rat isolated perfused kidney, microdissected glomeruli, and isolated juxtaglomerular cells is inhibited by endogenous or overexpressed cGMP-dependent protein kinases. Proc. Natl. Acad. Sci. USA 1998; 95: 9003 ? 9008, (scientific article)
- Fassnacht M, Hahner S, Beuschlein F, Klinik A, Reincke M, Allolio B.
(2000). New mechanisms of adrenostatic compounds in a human adrenocortical cancer cell line. Eur J Clin Invest. 2000; 30: 76-82, (scientific article)
Links:
Deutsche Forschungsgemeinschaft
