Ligand-induced endocytosis and nuclear localization of angiotensin II receptors expressed in CHO cells

Merjan, A.j.; Kanashiro, Célia A.; Krieger, José Eduardo; Han, Sang Won; Paiva, Antonio Cechelli de Mattos

doi:10.1590/s0100-879x2001000900011

Cited by 16 publications

(9 citation statements)

References 30 publications

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“…(55) Confocal microscopy demonstrated that functional fluorescent-labelled At-1 receptors traffic to the nuclear interior upon agonist binding. (54,56) Moreover, direct administration of angiotensin or renin into the intracellular space produced alterations in calcium flux and conductance in cardiac myocytes. (1) In addition to a local tissue RAS system, the adrenal has been reported to employ an intracellular RAS that appears to regulate aldosterone synthesis following nephrectomy.…”

Section: The Nature Of Intracrinesmentioning

confidence: 99%

“…In this regard, it should be noted that it has not been shown that losartan is not internalized in spite of implications to that effect in the literature. (6,20,54,56) Indeed, recently robust internalization of angiotensin II receptors following the administration of losartan has been reported. (56) Also of interest is the demonstration that these hepatoma cells expressed socalled exon-1A renin-a transcript predicted to produce an active renin (as opposed to prorenin) and to remain intracellular because it lacks a secretory signal sequence.…”

Section: The Nature Of Intracrinesmentioning

confidence: 99%

“…(6,20,54,56) Indeed, recently robust internalization of angiotensin II receptors following the administration of losartan has been reported. (56) Also of interest is the demonstration that these hepatoma cells expressed socalled exon-1A renin-a transcript predicted to produce an active renin (as opposed to prorenin) and to remain intracellular because it lacks a secretory signal sequence. (53,57) Taken together, these findings point to the existence of intracrine angiotensin action and, indeed, again raise the possibility that a complete intracrine RAS (iRAS) exists in some cells.…”

Section: The Nature Of Intracrinesmentioning

confidence: 99%

“…(8) This kind of homeoprotein developmental signaling is reminiscent of the action of certain plant transcription factors that travel between cells via plasmodesmata and influence transcription/development in the target cells. (24,25,56) The intracrine origin hypothesis attempts to structure this and similar data by assuming that the progenitors of the intracrines were proteins synthesized as multiple isoforms some of which stimulated trophic activity, some of which regulated the protein synthetic apparatus in coordination with that activity, and some of which generated feed-back loops to amplify and sustain (remember) that activity. With the advent of metazoans, the transfer of isoforms of intracrine progenitors to nearby cells either by transiting intercellular channels (viz plasmodesmata) or by one form of secretion or another, could produce a coordinated trophic effect, upregulation of the protein synthetic machinery, and memory in an entire tissue (Fig.…”

Section: Intracrine Biology and Developmentmentioning

confidence: 99%

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The intracrine hypothesis and intracellular peptide hormone action

Ré

2003

BioEssays

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There is evidence that many peptide growth factors and hormones act in the intracellular space after either internalization or retention in their cells of synthesis. These factors, commonly called intracrines, are structurally diverse while sharing some common functional features. Reports of intracellular peptide hormone binding and action are reviewed here. Also, this laboratory has made proposals regarding the origin and actions of intracrines and these areas are further explored. Intracrine interactions and the relationship of intracrines to transcription factors are discussed. The intracellular/intracrine renin-angiotensin system (iRAS) is reviewed to illustrate the intracrine analogue of a well-established physiological system. The role of intracrine action in metazoan development is also considered.

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Section: The Nature Of Intracrinesmentioning

confidence: 99%

Section: The Nature Of Intracrinesmentioning

confidence: 99%

Section: The Nature Of Intracrinesmentioning

confidence: 99%

Section: Intracrine Biology and Developmentmentioning

confidence: 99%

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The intracrine hypothesis and intracellular peptide hormone action

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2003

BioEssays

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“…7 These observations again raise the possibility that complete intracellular renin-angiotensin systems exist in some cells. [13][14][15][32][33][34][35][36] These intracrine renin-angiotensin systems (iRAS) could offer a new therapeutic target, given the differential ability of various inhibitors to act at intracellular sites. Parenthetically, regulatory loops linking the iRAS components angiotensinogen with p53 and renin with nucleolin mirror the regulatory relations of other intracrines with p53 and nucleolin.…”

Section: Intracrine Prorenin/reninmentioning

confidence: 99%

Intracellular Renin and the Nature of Intracrine Enzymes

Ré

2003

Hypertension

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Abstract-Recently, the binding of renin and prorenin to cellular receptors with the subsequent generation of second messengers and the production of physiological effects has been demonstrated. In addition, the internalization of prorenin by target cells has been associated with increased cellular synthesis of angiotensin and cardiac pathology. Also, a renin transcript lacking the sequences encoding a secretory signal has been reported, and this transcript appears to produce a renin that acts in the cell that synthesized it. Some years ago, we coined the term intracrine for a peptide hormone or factor that acts in the intracellular space either after internalization or retention in its cell of synthesis. Thus defined, a wide variety of peptides display intracrine functionality, including hormones, growth factors, transcription factors, and enzymes. For example, considerable evidence indicates that angiotensin II is an intracrine. Also, general principles of intracrine functionality have been developed. Thus, recent evidence demonstrates that the prorenin/renin molecule is an intracrine enzyme. Here, the actions of intracrine enzymes (angiogenin, phosphoglucose isomerase, phospholipase A2, granzyme A and B, thioredoxin, platelet-derived endothelial growth factor, and serine protease inhibitors) are reviewed. Key Words: renin Ⅲ platelet-derived growth factor Ⅲ enzymes Ⅲ angiotensin II Ⅲ phospholipases R enin gene expression leads to the synthesis of prorenin in the juxtaglomerular cells of the kidney, activation and secretion of renin by these cells, the generation of angiotensin I by renin enzymatic activity, and the subsequent generation of angiotensin II either in the plasma or tissues. However, renin, angiotensin I, and angiotensin II can also be taken up by tissues with subsequent enzymatic conversions occurring locally. Moreover, there is considerable evidence, both in animal models and in humans, in favor of the local synthesis of each of the components of the renin-angiotensin system (RAS) in various tissues leading to locally determined angiotensin generation. 1 In addition to evidence indicating local synthesis and uptake in tissues of RAS components, there is growing evidence to indicate the uptake and synthesis of components of the RAS by individual cells, thereby suggesting a new arena for the action of this physiological system. 2 Important among these new observations are studies demonstrating that (1) prorenin and renin can bind to specific cellular receptors with the generation of physiological effects, (2) prorenin, and to a lesser extent, renin, can be internalized by cells whereupon angiotensin II is produced, and (3) there exists a renin transcript in some cells that encodes a renin that is expected to be synthesized as an active, as opposed to a prorenin, and that is expected to remain in the cell because it lacks the sequence encoding the secretory signal piece (renin exon 1A). 2-13 These observations not only reveal prorenin and renin to be hormones in their own right, they suggest that pro...

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Different protective actions of losartan and tempol on the renal inflammatory response to acute sodium overload

Rosón

Penna

Cao

et al. 2010

Journal Cellular Physiology

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The aim of this work was to study the role of local intrarenal angiotensin II (Ang II) and the oxidative stress in the up-regulation of pro-inflammatory cytokines expression observed in rats submitted to an acute sodium overload. Sprague-Dawley rats were infused for 2 h with isotonic saline solution (Control group) and with hypertonic saline solution alone (Na group), plus the AT1 receptor antagonist losartan (10 mg kg(-1) in bolus) (Na-Los group), or plus the superoxide dismutase mimetic tempol (0.5 mg min(-1) kg(-1)) (Na-Temp group). Mean arterial pressure, glomerular filtration rate, and fractional sodium excretion (FE(Na)) were measured. Ang II, NF-kappaB, hypoxia inducible factor-1 alpha (HIF-1 alpha), transforming growth factor beta1 (TGF-beta1), smooth muscle actin (alpha-SMA), endothelial nitric oxide synthase (eNOS), and RANTES renal expression was evaluated by immunohistochemistry. Ang II, NF-kappaB, and TGF-beta1 and RANTES early inflammatory markers were overexpressed in Na group, accompanied by enhanced HIF-1 alpha immunostaining, lower eNOS expression, and unmodified alpha-SMA. Losartan and tempol increased FE(Na) in sodium overload group. Although losartan reduced Ang II and NF-kappaB staining and increased eNOS expression, it did not restore HIF-1 alpha expression and did not prevent inflammation. Conversely, tempol increased eNOS and natriuresis, restored HIF-1 alpha expression, and prevented inflammation. Early inflammatory markers observed in rats with acute sodium overload is associated with the imbalance between HIF-1 alpha and eNOS expression. While both losartan and tempol increased natriuresis and eNOS expression, only tempol was effective in restoring HIF-1 alpha expression and down-regulating TGF-beta1 and RANTES expression. The protective role of tempol, but not of losartan, in the inflammatory response may be associated with its greater antioxidant effects.

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Ligand-induced endocytosis and nuclear localization of angiotensin II receptors expressed in CHO cells

Cited by 16 publications

References 30 publications

The intracrine hypothesis and intracellular peptide hormone action

The intracrine hypothesis and intracellular peptide hormone action

Intracellular Renin and the Nature of Intracrine Enzymes

Different protective actions of losartan and tempol on the renal inflammatory response to acute sodium overload

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