Intracellular ANG II induces cytosolic Ca<sup>2+</sup>mobilization by stimulating intracellular AT<sub>1</sub>receptors in proximal tubule cells

Zhuo, Jia L.; Li, Xiao C.; Garvin, Jeffrey L.; Navar, L. Gabriel; Carretero, Oscar A.

doi:10.1152/ajprenal.00269.2005

Cited by 90 publications

(123 citation statements)

References 40 publications

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“…This increase was prevented by a cellpermeable analog of an ETB-selective antagonist, IRL-2500, but not by adding BQ610 and BQ788 to the extracellular medium, thus confirming a direct role of nuclear ETB in regulating nuclear Ca 2+ signalling in intact ventricular myocytes. Other GPCRs found in nuclear membranes have also been show to increase [Ca 2+ ] n including Ang II [18,91], bradykinin B2 [21], prostaglandin E 2 [22][23][24], lysophosphatidic acid type-1 [25,26], and metabotropic glutamate type-5 [92][93][94][95].…”

Section: Discussionmentioning

confidence: 99%

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Merlen¹,

Farhat²,

Luo³

et al. 2013

Journal of Molecular and Cellular Cardiology

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Endothelin receptors are present on the nuclear membranes in adult cardiac ventricular myocytes. The objectives of the present study were to determine 1) which endothelin receptor subtype is in cardiac nuclear membranes, 2) if the receptor and ligand traffic from the cell surface to the nucleus, and 3) the effect of increased intracellular ET-1 on nuclear Ca 2+ signalling. Confocal microscopy using fluorescently-labeled endothelin analogs confirmed the presence of ETB at the nuclear membrane of rat cardiomyocytes in skinned-cells and isolated nuclei. Furthermore, in both cardiac myocytes and aortic endothelial cells, endocytosed ET:ETB complexes translocated to lysosomes and not the nuclear envelope. Although ETA and ETB can form heterodimers, the presence or absence of ETA did not alter ETB trafficking. Treatment of isolated nuclei with * Abbreviations: The abbreviations used are: 2-APB, 2-aminoethoxydiphenyl borate; A, Angiotensin II; αAR, α-adrenergic receptor;[Ca 2+ ] n , nucleoplasmic free calcium concentration; CaMKII, Ca 2+ /calmodulin-dependent protein kinase II; DMNB, 4,5-dimethoxynitrobenzyl group; DNA, deoxyribonucleic acid; DCC, 1,3-dicyclohexylcarbodiimide; DCM, dichloromethane; DTT, dithiothreitol; ECE1-a, endothelin converting enzyme 1a; cET-1, caged ET-1; caged ET-1, [Trp-ODMNB 21 ]ET-1; ET-1, endothelin 1; ET-2, endothelin 2; ET-3, endothelin 3; ETA, endothelin type A receptor; ETB, endothelin type B receptor; ETR, endothelin receptor; GPCR, G protein-coupled receptor; HDAC5; histone deacetylase 5; IP3, inositol 1,4,5-trisphosphate; IP3R, inositol 1,4,5-trisphosphate receptor; ISO, isoproterenol; MEF2, myocyte enhancing factor-2; PBS, phosphate buffered saline; PMSF, phenylmethanesulphonylfluoride; PNGase F, peptide N-glycosidase F; qPCR, quantitative real-time polymerase chain reaction; RNA, ribonucleic acid; RyR, ryanodine receptor; TCA, trichloroacetic acid; TFA, trifluoroacetic acid; TX-100, Triton X-100. Address correspondence to: Bruce G. Allen, Montreal Heart Institute, 5000 Belanger St,. Montréal, Québec, Canada, H1T 1C8., Telephone: (514) ] n whereas extracellular application of ETA and ETB receptor antagonists did not. These data suggest that 1) the endothelin receptor in the cardiac nuclear membranes is ETB, 2) ETB traffic directly to the nuclear membrane after biosynthesis, 3) exogenous endothelins are not ligands for ETB on nuclear membranes, and 4) ETB associated with the nuclear membranes regulate nuclear Ca 2+ signalling.

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Section: Discussionmentioning

confidence: 99%

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Merlen¹,

Farhat²,

Luo³

et al. 2013

Journal of Molecular and Cellular Cardiology

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“…37,52,63,70,71 Activation of AT 1 -receptors leads to phosphoinositide hydrolysis, mobilisation of intracellular calcium, and inhibition of adenylate cyclase. 38,45,46,57,72,73 By contrast, only low levels of AT 2 -receptors are expressed in proximal tubules and the role of this receptor is much less clearly defined than that of the AT 1 -receptor. 57,60,[74][75][76] The classic view of Ang II-mediated actions is that Ang II binds its receptors at the plasma membrane and phosphorylation of the receptor…”

Section: Overview Of Proximal Tubule Reninangiotensin Systemmentioning

confidence: 99%

“…Intracellular kinases activated by Ang II include extracellular signal-regulated protein kinase(s) (ERKs) 63,70,117,122 JAK-STAT signalling 117,123,124 and calcineurin phosphatase. 126,127 Internalised Ang II may also be translocated to the nucleus, 20,97,99,110 where it may activate nuclear calcium 28,29,45 and stimulate transcription of NHE-3 and pro-inflammatory cytokines and growth factors. 20,47,69,97,111,128 Recent studies indicate that Ang II activates nuclear transcription factor NF-κB and activator protein-1 (AP-1) in the kidney, leading to longlasting inflammatory and growth-promoting effects.…”

Section: O P Y R I G H T J R a A S L I M I T E D R E P R O D U C T mentioning

confidence: 99%

Review: Novel roles of intracrine angiotensin II and signalling mechanisms in kidney cells

Zhuo

2007

J Renin Angiotensin Aldosterone Syst

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Angiotensin II (Ang II) has powerful sodiumretaining, growth-promoting and proinflammatory properties in addition to its physiological role in maintaining body salt and fluid balance and blood pressure homeostasis. Increased circulating and local tissue Ang II is one of the most important factors contributing to the development of sodium and fluid retention, hypertension and target organ damage.The importance of Ang II in the pathogenesis of hypertension and target organ injury is best demonstrated by the effectiveness of angiotensinconverting enzyme (ACE) inhibitors and AT 1 -receptor antagonists in treating hypertension and progressive renal disease including diabetic nephropathy.The detrimental effects of Ang II are mediated primarily by the AT 1 -receptor, while the AT 2 -receptor may oppose the AT 1 -receptor. The classical view of the AT 1 -receptor-mediated effects of Ang II is that the agonist binds its receptors at the cell surface, and following receptor phosphorylation, activates downstream signal transduction pathways and intracellular responses. However, evidence is emerging that binding of Ang II to its cell surface AT 1 -receptors also activates endocytotic (or internalisation) processes that promote trafficking of both the effector and the receptor into intracellular compartments.Whether internalised Ang II has important intracrine and signalling actions is not well understood.The purpose of this article is to review recent advances in Ang II research with focus on the mechanisms underlying high levels of intracellular Ang II in proximal tubule cells and the contribution of receptor-mediated endocytosis of extracellular Ang II. Further attention is devoted to the question whether intracellular and/or internalised Ang II plays a physiological role by activating cytoplasmic or nuclear receptors in proximal tubule cells.This information may aid future development of drugs to prevent and treat Ang II-induced target organ injury in cardiovascular and renal diseases by blocking intracellular and/or nuclear actions of Ang II.

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“…We previously reported that intracellular administration of angiotensin II via liposomes increases contractility of rat aorta via activation of intracellular receptors (7). Similarly, microinjection of angiotensin II increases cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] i ) in vascular smooth muscle cells (13,16) or kidney proximal tubule cells (49). The intracellular angiotensin II can result either via uptake from the interstitium or by intracellular synthesis.…”

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confidence: 99%

Intracellular angiotensin II activates rat myometrium

Deliu

Tica

Motoc

et al. 2011

American Journal of Physiology-Cell Physiology

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Deliu E, Tica AA, Motoc D, Brailoiu GC, Brailoiu E. Intracellular angiotensin II activates rat myometrium. Am J Physiol Cell Physiol 301: C559 -C565, 2011. First published May 22, 2011; doi:10.1152/ajpcell.00123.2011.-Angiotensin II is a modulator of myometrial activity; both AT1 and AT2 receptors are expressed in myometrium. Since in other tissues angiotensin II has been reported to activate intracellular receptors, we assessed the effects of intracellular administration of angiotensin II via microinjection on myometrium, using calcium imaging. Intracellular injection of angiotensin II increased cytosolic Ca 2ϩ concentration ([Ca 2ϩ ]i) in myometrial cells in a dose-dependent manner. The effect was abolished by the AT 1 receptor antagonist losartan but not by the AT2 receptor antagonist PD-123319. Disruption of the endo-lysosomal system, but not that of Golgi apparatus, prevented the angiotensin II-induced increase in [Ca 2ϩ ]i. Blockade of AT1 receptor internalization had no effect, whereas blockade of microautophagy abolished the increase in [Ca 2ϩ ]i produced by intracellular injection of angiotensin II; this indicates that microautophagy is a critical step in transporting the peptide into the endo-lysosomes lumenum. The response to angiotensin II was slightly reduced in Ca 2ϩ -free saline, indicating a major involvement of Ca 2ϩ release from internal stores. Blockade of inositol 1,4,5-trisphosphate (IP 3) receptors with heparin and xestospongin C or inhibition of phospholipase C (PLC) with U-73122 abolished the response to angiotensin II, supporting the involvement of PLC-IP 3 pathway. Angiotensin II-induced increase in [Ca 2ϩ ]i was slightly reduced by antagonism of ryanodine receptors. Taken together, our results indicate for the first time that in myometrial cells, intracellular angiotensin II activates AT 1-like receptors on lysosomes and activates PLC-IP 3-dependent Ca 2ϩ release from endoplasmic reticulum; the response is further augmented by a Ca 2ϩ -induced Ca 2ϩ release mechanism via ryanodine receptors activation. calcium imaging; cytosolic calcium concentration; endoplasmic reticulum; microinjection ANGIOTENSIN II is an eight amino acid peptide that exerts its actions by activation of G protein-coupled receptors, namely AT 1 and AT 2 receptors. Increasing evidence suggests that angiotensin II acts not only as an endocrine/paracrine factor, but also as an autacoid or intracrine peptide, with the ability to signal from within the cell, without stimulating plasma membrane receptors (21, 38). We previously reported that intracellular administration of angiotensin II via liposomes increases contractility of rat aorta via activation of intracellular receptors (7). Similarly, microinjection of angiotensin II increases cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] i ) in vascular smooth muscle cells (13, 16) or kidney proximal tubule cells (49). The intracellular angiotensin II can result either via uptake from the interstitium or by intracellular synthesis. In the latter case, intracellular renin conver...

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Intracellular ANG II induces cytosolic Ca²⁺mobilization by stimulating intracellular AT₁receptors in proximal tubule cells

Cited by 90 publications

References 40 publications

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Review: Novel roles of intracrine angiotensin II and signalling mechanisms in kidney cells

Intracellular angiotensin II activates rat myometrium

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Intracellular ANG II induces cytosolic Ca2+mobilization by stimulating intracellular AT1receptors in proximal tubule cells

Cited by 90 publications

References 40 publications

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Review: Novel roles of intracrine angiotensin II and signalling mechanisms in kidney cells

Intracellular angiotensin II activates rat myometrium

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Intracellular ANG II induces cytosolic Ca²⁺mobilization by stimulating intracellular AT₁receptors in proximal tubule cells