[PP.25.06] ANGIOTENSIN-(1–7) PEPTIDE AND MAS RECEPTOR AND ANGIOTENSIN II- TYPE 2 RECEPTOR ARE INVOLVED IN ALDOSTERONE AND CORTISOL PRODUCTION IN HUMAN ADRENOCORTICAL CELL LINE (NCI-H295)

2016 ◽  
Vol 34 ◽  
pp. e267 ◽  
Author(s):  
P. Vanderriele ◽  
B. Caroccia ◽  
L. Lenzini ◽  
F. Giocco ◽  
A. Fassina ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cell Line ◽  
Adrenocortical Cell ◽  
Mas Receptor

The angiotensin II type 1 receptor-neprilysin inhibitor LCZ696 blocked aldosterone synthesis in a human adrenocortical cell line

2016 ◽  
Vol 39 (11) ◽  
pp. 758-763 ◽  
Author(s):  
Shin-Ichiro Miura ◽  
Yasunori Suematsu ◽  
Yoshino Matsuo ◽  
Sayo Tomita ◽  
Asuka Nakayama ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cell Line ◽  
Adrenocortical Cell ◽  
Neprilysin Inhibitor

scholarly journals Transforming growth factor beta1 inhibits aldosterone and cortisol production in the human adrenocortical cell line NCI-H295R through inhibition of CYP11B1 and CYP11B2 expression

2003 ◽  
Vol 176 (1) ◽  
pp. 69-82 ◽  
Author(s):  
P Liakos ◽  
D Lenz ◽  
R Bernhardt ◽  
JJ Feige ◽  
G Defaye
Keyword(s):  
Angiotensin Ii ◽  
Growth Factor ◽  
Tumor Cell ◽  
Cell Line ◽  
Transforming Growth Factor ◽  
Tumor Cell Line ◽  
Mrna Levels ◽  
Adrenocortical Tumor ◽  
Adrenocortical Cell ◽  
Transforming Growth Factor Beta1

Transforming growth factor beta1 (TGFbeta1) has been shown to exert strong inhibitory effects on adrenocortical cell steroidogenesis. However, the molecular targets of TGFbeta1 in adrenocortical cells appear to differ between species. Here, we report the first characterization of the regulatory effects of TGFbeta1 on the steroidogenic functions of the human adrenocortical tumor cell line NCI-H295R. After treatment with 2 ng/ml TGFbeta1 for 24 h, basal production of corticosterone, cortisol and androstenedione was dramatically decreased. When TGFbeta1 was added simultaneously with forskolin, the production of cortisol and 11-hydroxyandrostenedione was decreased by 85% whereas that of deoxycortisol was increased. When TGFbeta1 was added simultaneously with angiotensin II, aldosterone production was reduced by 80%. We observed that TGFbeta1 strongly inhibits forskolin-induced steroid 11beta-hydroxylase activity and CYP11B1 mRNA levels, as well as angiotensin II-induced aldosterone synthase activity and CYP11B2 mRNA levels. CYP11B1 and CYP11B2 gene products thus appear as the major steroidogenic enzymes down-regulated by TGFbeta1 in the human adrenocortical tumor cell line NCI-H295R.

Abstract 639: Angiotensin 1-7 Contributes To Cardioprotective Effects Of Cardiac Overexpression Of Angiotensin II Type 2 Receptor In Mice Post-MI

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Jiang Xu ◽  
Oscar A Carretero ◽  
Liping Zhu ◽  
Pamela Harding ◽  
Nour-Eddine Rhaleb ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Capillary Density ◽  
Left Ventricular ◽  
Ang Ii ◽  
Wild Type ◽  
Cross Sectional ◽  
Mas Receptor ◽  
Cardioprotective Effects ◽  
Mini Pump

Angiotensin II (Ang II) acting on AT1 receptor plays a pivotal role in the pathophysiology of cardiovascular disease, whereas AT2 has been considered cardioprotective, although the mechanisms are not fully understood. Recently studies suggest AT2 interacts with ACE2, an enzyme known to release Ang 1-7 from Ang II. Thus we hypothesize that Ang 1-7 contributes to cardioprotective effects of AT2, possibly via AT2/ACE2/Ang 1-7 cascade. Transgenic mice with AT2 specifically overexpressed in the heart (Tg-AT2) and their wild-type littermates (WT) were subjected to myocardial infarction (MI) or sham MI and divided into 1) sham MI; 2) MI + vehicle; and 3) MI + Mas receptor antagonist ([D-Ala7-Ang 1-7], A779, 0.5 mg/kg/day via osmotic mini pump). Treatments were started on the same day of MI and continued for 8 weeks. Our data show that AT2 and ACE2 protein expression in the heart was significantly increased in Tg-AT2 mice, whereas AT1 protein remained unchanged. Systolic blood pressure (SBP) and cardiac phenotypes did not differ between strains under basal conditions. MI increased myocyte cross-sectional area (MCSA), interstitial collagen fraction (ICF), left ventricular diastolic dimension (LVDd) and capillary density, and decreased LV ejection fraction (EF) in both strains; however, these pathological responses were diminished in Tg-AT2. Blockade of Mas receptor with A779 attenuated the cardioprotective effects observed in Tg-AT2 mice (Table). Infarct size (IS) did not differ among groups. Our findings suggest that overexpression/activation of AT2 protects against cardiac remodeling and dysfunction post MI, which is mediated in part through Ang 1-7 acting on the Mas receptor.

scholarly journals Angiotensin II type 1 receptor blockers favorably affect renal angiotensin II and MAS receptor expression in patients with diabetic nephropathy

2020 ◽  
Vol 21 (2) ◽  
pp. 147032032091960 ◽  
Author(s):  
Ye-Ping Ma ◽  
Yue Yang ◽  
Shi-Min Jiang ◽  
Lin Liu ◽  
Zheng Zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Angiotensin Ii ◽  
Protein Expression ◽  
Renal Biopsy ◽  
Expression Levels ◽  
Mas Receptor ◽  
Class Iib ◽  
Renal Expression

Introduction: The aims of this study were to assess the renal expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor in human type 2 diabetic nephropathy (DN). Materials and methods: In total, 115 patients diagnosed with DN by renal biopsy were enrolled in this study. The protein expression levels of the AT1R, AT2R, and MAS receptors were assessed by immunohistochemistry. Results: The protein expression levels of AT1R, AT2R, and MAS receptor in the renal biopsy tissue were correlated with the pathologic classification of DN. Tubulointerstitial AT1R expression in patients of class IIb was significantly stronger than control samples ( p < 0.05). Expression of AT2R and MAS receptors were highest with class IIb DN patients. When DN patients were treated with AT1R blocker (ARB), the expression of AT1R was downregulated ( p < 0.05), and the MAS receptor was upregulated in tubular interstitial ( p < 0.05). Conclusions: Our results directly observed that renal expression levels of AT1R increase during the early stages of DN, ARB reducing AT1R while increasing MAS receptor. Therefore, ARB should be used as soon as possible in patients with DN.

scholarly journals Microribonucleic Acid-21 Increases Aldosterone Secretion and Proliferation in H295R Human Adrenocortical Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2477-2483 ◽  
Author(s):  
Damian G. Romero ◽  
Maria W. Plonczynski ◽  
Cristian A. Carvajal ◽  
Elise P. Gomez-Sanchez ◽  
Celso E. Gomez-Sanchez
Keyword(s):  
Cell Proliferation ◽  
Angiotensin Ii ◽  
Cell Line ◽  
Biologically Active ◽  
Cell Physiology ◽  
Adrenocortical Cell ◽  
Aldosterone Secretion ◽  
Adrenocortical Cells ◽  
Expression Levels ◽  
H295r Cells

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that decrease the expression levels of specific genes by translational repression, sequestration, and degradation of their mRNAs. Angiotensin II is an important modulator of adrenal zona glomerulosa cell physiology, including steroidogenesis and proliferation among many other physiological processes. Because each miRNA may regulate the expression levels of multiple genes, thereby resembling the transcription regulatory networks triggered by transcription factors, we hypothesize that specific miRNAs may be involved in angiotensin II-mediated adrenocortical cell physiology. The human adrenocortical cell line H295R is the only adrenal cell line available with a steroid secretion pattern and regulation similar to freshly isolated adrenocortical cells. We screened for miRNAs regulated by angiotensin II in H295R cells and found that miRNA-21 expression levels were specifically modulated by angiotensin II. Angiotensin II time dependently increased miRNA-21 expression reaching a 4.4-fold induction after 24 h. Angiotensin II-mediated miRNA-21 expression resulted in biologically active miRNA-21, determined using a fusion mRNA reporter system carrying miRNA-21 target sequences in its 3′ untranslated region. Up-regulation of miRNA-21 intracellular levels increased aldosterone secretion but not cortisol. Elevation of miRNA-21 levels also increased cell proliferation in H295R cells. In summary, miRNA-21 is an endogenously expressed miRNA in human adrenal cells. miRNA-21 expression is up-regulated by angiotensin II, and its overexpression caused an increase in aldosterone secretion and cell proliferation. Alterations in miRNA-21 expression levels or function may be involved in dysregulation of angiotensin II signaling and abnormal aldosterone secretion by adrenal glands in humans.

scholarly journals Angiotensin II and III Metabolism and Effects on Steroid Production in the HAC15 Human Adrenocortical Cell Line

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 214-221 ◽  
Author(s):  
Kenji Oki ◽  
Phillip G. Kopf ◽  
William B. Campbell ◽  
Milay Luis Lam ◽  
Takeshi Yamazaki ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cell Line ◽  
Regulatory Protein ◽  
Renin Angiotensin System ◽  
Hydroxysteroid Dehydrogenase ◽  
Zona Glomerulosa ◽  
Cortisol Secretion ◽  
Adrenocortical Cell ◽  
Aldosterone Secretion ◽  
Steroidogenic Acute Regulatory

Aldosterone is synthesized in the zona glomerulosa of the adrenal cortex under primary regulation by the renin-angiotensin system. Angiotensin II (A-II) acts through the angiotensin types 1 and 2 receptors (AT1R and AT2R). A-II is metabolized in different tissues by various enzymes to generate two heptapeptides A-III and angiotensin 1-7, which can then be catabolized into smaller peptides. A-II was more potent than A-III in stimulating aldosterone secretion in the adrenocortical cell line HAC15, and A-II, but not A-III, stimulated cortisol secretion. A-II stimulated mRNA expression of steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, CYP11B1, and CYP11B2, whereas A-III stimulated 3β-hydroxysteroid dehydrogenase, CYP11B1, and CYP11B2 but decreased the expression of CYP17A1 required for cortisol synthesis. The stimulation of aldosterone secretion by A-II and A-III was blocked by the AT1R receptor blocker, losartan, but not by an AT2R blocker. A-II was rapidly metabolized by the HAC15 cells to mainly to angiotensin 1-7, but not to A-III, and disappeared from the supernatant within 6 h. A-III was metabolized rapidly and disappeared within 1 h. In conclusion, A-II was not converted to A-III in the HAC15 cell and is the more potent stimulator of aldosterone secretion and cortisol of the two. A-III stimulated aldosterone secretion but not cortisol secretion.

Sign in / Sign up

Export Citation Format

Share Document