Mechanisms of vascular angiotensin II surface receptor regulation by epidermal growth factor

Ullian, Michael E.; Webb, Jerry G.; Chen, Ruihua; Paul, Richard V.; Morinelli, Thomas A.

doi:10.1002/jcp.20027

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…Movement of AT 1 receptors in and out of the cell surface is well-described and involves interactions with microtubules and other cytoskeleton elements (15,29,32). In the present study, the addition of the microtubular depolymerizing agent colchicine prevented the enhanced response of proximal tubule cells preincubated at pH 7.0 to ANG II and also disrupted the enhancement of cell surface expression of AT 1 receptors by low pH.…”

Section: Discussionsupporting

confidence: 50%

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

Nagami

Chang²,

Plato³

et al. 2008

American Journal of Physiology-Renal Physiology

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Nagami GT, Chang JA, Plato ME, Santamaria R. Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II. Am J Physiol Renal Physiol 295: F1864 -F1870, 2008. First published October 22, 2008 doi:10.1152/ajprenal.90410.2008.-The proximal tubule defends the body against acid challenges by enhancing its production and secretion of ammonia. Our previous studies demonstrated an enhanced ammoniagenic response of the proximal tubule to ANG II added to the lumen in vitro after an in vivo acid challenge. The present study examined the effect of NH 4Cl acid loading in vivo on renal cortical type 1 ANG II (AT 1) receptor expression, the effect of low pH on AT 1 receptor expression in a proximal tubule cells in culture, and their response to ANG II. A short-term (18 h) NH 4Cl load in vivo resulted in increased renal cortical AT 1 receptor mRNA expression and increased brush-border membrane AT 1 receptor protein expression levels. Changing the cell culture pH from 7.4 to 7.0 for at least 2 h increased cell surface expression of AT 1 receptors and enhanced the stimulatory effect of ANG II on ammonia production rates. This increased ammoniagenic response to ANG II and the early enhancement of cell surface expression induced by exposure of the cultured proximal tubule cells to pH 7.0 were prevented by treatment with colchicine. These results suggest that, after acid challenges, the enhanced ammoniagenic response of the proximal tubule to ANG II is, in part, mediated by increased AT 1 receptor cell surface expression and that the enhancement of receptor expression plays an important role in the early response of the proximal tubule to acid challenges. ammoniagenesis; angiotensin type receptor; cell surface; acidosis; colchicine THE PROXIMAL TUBULE PLAYS an important role in defending the body against acid challenges by producing and secreting tNH 3 (tNH 3 ϭ NH 4 ϩ ϩ NH 3 ) (21). Renal tNH 3 production and excretion are enhanced in response to acid challenges (28, 30), and the major site of the increase in tNH 3 production and secretion rates that occur in response to acid challenges is the proximal tubule (21).ANG II plays an important role in the regulation of tNH 3 production by the proximal tubule (4,19,20,22). When tested in vitro, ANG II has concentration-dependent effects on tNH 3 production and transport by the proximal tubule (19,20). The stimulatory effect of ANG II on tNH 3 production rates is mediated by type 1 ANG II (AT 1 ) receptors, and this stimulatory effect is enhanced in proximal tubule segments derived from acid-loaded mice (22)(23)(24).Using in vitro microperfused mouse proximal tubules, we previously demonstrated that a short-term (18 h) NH 4 Cl acid challenge in vivo resulted in an increased stimulatory effect of ANG II on tNH 3 production (22). Nevertheless, it was unclear whether upregulation of the systemic renin-angiotensin system with acid loading (9, 10, 27) was responsible for the increased ammoniagenic response to ANG II of...

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Section: Discussionsupporting

confidence: 50%

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

Nagami

Chang²,

Plato³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…To determine if the active form of APC was needed to increase sprout formation, aortic sections were also treated with PC (10 μg/mL) with or without hirudin (50 nM) or APC-DEGR (10 μg/mL). In studies looking at EGFR, PI3K, and MMPs, pharmacological inhibitors, AG 1478 (10 μM;Biomol) [25], LY 294002 (10 μg/mL; Biomol) [26], and GM 6001 (10 μg/mL;Biomol) [27], respectively, were added to the aortic sections 30 minutes prior to the addition of APC (10 μg/mL). Every 24 h for 5 days, media from each well was removed and replaced with fresh conditioned media.…”

Section: Methodsmentioning

confidence: 99%

Activated protein C enhances cell motility of endothelial cells and MDA-MB-231 breast cancer cells by intracellular signal transduction

Gramling¹,

Beaulieu²,

Church³

2010

Experimental Cell Research

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Activated protein C (APC), an anticoagulant serine protease, has been shown to have non-hemostatic functions related to inflammation, cell survival, and cell migration. In this study we investigate the mechanism by which APC promotes angiogenesis and breast cancer invasion using ex vivo and in vitro methods. When proteolytically active, APC promotes cell motility/invasion and tube formation of endothelial cells. Ex vivo aortic ring assays verify the role of APC in promoting angiogenesis, which was determined to be dependent on EGFR and MMP activation. Given the capacity of APC to promote angiogenesis and the importance of this process in cancer pathology, we investigated whether the mechanisms by which APC promotes angiogenesis can also promote motility and invasion in the MDA-MB-231 breast cancer cell line. Our results indicate that, extracellularly, APC engages EPCR, PAR-1, and EGFR in order to increase the invasiveness of MDA-MB-231 cells. APC activation of matrix metalloprotease (MMP) -2 and/or -9 is necessary but not sufficient to increase invasion, and APC does not utilize the endogenous plasminogen activation system to increase invasion. Intracellularly, APC activates ERK, Akt, and NFκB, but not the JNK pathway to promote MDA-MB-231 cell motility. Similar to the hemostatic protease thrombin, APC has the ability to enhance both endothelial cell motility/angiogenesis and breast cancer cell migration.

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“…Treatment with EGF and bFGF causes down-regulation of the AT 1 R (Nickenig and Murphy, 1994;Ullian et al, 1997) and consequent reduction of Ang II-induced InsP production (Ullian et al, 2004). In addition, activation of EGF-R, PDGF-R, and insulin receptor signaling initiates intracellular pathways that inhibit the actions of ␣ 1b -adrenergic receptors (␣ 1b -ARs) by promoting their phosphorylation and decreasing their coupling to heterotrimeric G proteins (Medina et al, 2000;García-Sá inz et al, 2004).…”

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confidence: 99%

Agonist-Induced Interactions between Angiotensin AT1 and Epidermal Growth Factor Receptors

Olivares-Reyes

Shah

Hernandez-Aranda

et al. 2005

Molecular Pharmacology

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In rat hepatic C9 cells, angiotensin II (Ang II)-induced activation of angiotensin type 1 (AT 1 ) receptors (AT 1 -Rs) stimulates extracellular signal-regulated kinase (ERK) 1/2 phosphorylation via transactivation of the endogenous epidermal growth factor (EGF) receptor (EGF-R) by a protein kinase C (PKC) ␦/Src/Pyk2-dependent pathway. This leads to phosphorylation of the EGF-R as well as its subsequent internalization. On the other hand, EGF-induced activation of the EGF-R in C9 cells was found to cause phosphorylation of the AT 1 -R. This was prevented by selective inhibition of the intrinsic tyrosine kinase activity of the EGF-R by AG1478 [4-(3Ј-chloroanilino)-6,7-dimethoxy-quinazoline] and was reduced by inhibition of PKC and phosphoinositide 3-kinase. EGF-induced AT 1 -R phosphorylation was associated with a decrease in membrane-associated AT 1 -Rs and a reduced inositol phosphate response to Ang II. Agonist activation of endogenous AT 1 -Rs and EGF-Rs induced the formation of a multireceptor complex containing both the AT 1 -R and the transactivated EGF-R. The dependence of these responses on caveolin was indicated by the finding that cholesterol depletion of C9 cells abolished Ang II-induced inositol phosphate production, activation of Akt/PKB and ERK1/2, and AT 1 -R internalization. Confocal microscopy demonstrated that caveolin-1 was endogenously phosphorylated and was distributed on the plasma membrane in patches that undergo redistribution during Ang II stimulation. Agonist-induced phosphorylation and association of caveolin 1 with the AT 1 -R was observed, consistent with a scaffolding role of caveolin during transactivation of the EGF-R by Ang II. The EGF-induced AT 1 -R/caveolin association was abolished by AG1478, suggesting that activation of the EGF-R promotes the association of caveolin and the AT 1 -R.

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Mechanisms of vascular angiotensin II surface receptor regulation by epidermal growth factor

Cited by 6 publications

References 26 publications

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

Acid loading in vivo and low pH in culture increase angiotensin receptor expression: enhanced ammoniagenic response to angiotensin II

Activated protein C enhances cell motility of endothelial cells and MDA-MB-231 breast cancer cells by intracellular signal transduction

Agonist-Induced Interactions between Angiotensin AT1 and Epidermal Growth Factor Receptors

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