The angiotensin II type 1 receptor and receptor-associated proteins

Guo, Deng Fu; Sun, Yu; Hamet, Pavel; Inagami, Tadashi

doi:10.1038/sj.cr.7290083

Cited by 165 publications

(135 citation statements)

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“…3, B and C). It has been reported that a general acceleration of cellular endocytic pathways and agonist-induced endocytosis of some receptors (such as the angiotensin II receptor) does not affect the production of A␤ and ␥-secretase activity (49,50). Thus, internalization of PS-1 (␥-secretase) with the EP 4 receptor seems to enhance production of A␤ and ␥-secretase activity specifically.…”

Section: Contribution Of Co-internalization Of Ps-1 With the Ep 4 Recmentioning

confidence: 99%

Prostaglandin E2 Stimulates the Production of Amyloid-β Peptides through Internalization of the EP4 Receptor

Hoshino

Namba

Takehara

et al. 2009

Journal of Biological Chemistry

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Amyloid-␤ (A␤) peptides, generated by the proteolysis of ␤-amyloid precursor protein by ␤-and ␥-secretases, play an important role in the pathogenesis of Alzheimer disease. Inflammation is also important. We recently reported that prostaglandin E 2 (PGE 2 ), a strong inducer of inflammation, stimulates the production of A␤ through EP 2 and EP 4 receptors, and here we have examined the molecular mechanism. Activation of EP 2 and EP 4 receptors is coupled to an increase in cellular cAMP levels and activation of protein kinase A (PKA). We found that inhibitors of adenylate cyclase and PKA suppress EP 2 , but not EP 4 , receptor-mediated stimulation of the A␤ production. In contrast, inhibitors of endocytosis suppressed EP 4 , but not EP 2 , receptor-mediated stimulation. Activation of ␥-secretase was observed with the activation of EP 4 receptors but not EP 2 receptors. PGE 2 -dependent internalization of the EP 4 receptor was observed, and cells expressing a mutant EP 4 receptor lacking the internalization activity did not exhibit PGE 2 -stimulated production of A␤. A physical interaction between the EP 4 receptor and PS-1, a catalytic subunit of ␥-secretases, was revealed by immunoprecipitation assays. PGE 2 -induced internalization of PS-1 and co-localization of EP 4 , PS-1, and Rab7 (a marker of late endosomes and lysosomes) was observed. Co-localization of PS-1 and Rab7 was also observed in the brain of wild-type mice but not of EP 4 receptor null mice. These results suggest that PGE 2 -stimulated production of A␤ involves EP 4 receptor-mediated endocytosis of PS-1 followed by activation of the ␥-secretase, as well as EP 2 receptor-dependent activation of adenylate cyclase and PKA, both of which are important in the inflammation-mediated progression of Alzheimer disease. Alzheimer disease (AD)2 is the most common neurodegenerative disorder of the central nervous system and the leading cause of adult onset dementia. AD is characterized pathologically by the accumulation of tangles and senile plaques. Senile plaques are composed of the amyloid-␤ (A␤) peptides A␤40 and A␤42 (1, 2). To generate A␤, ␤-amyloid precursor protein (APP) is first cleaved by ␤-secretase and then by ␥-secretase. Cleavage of APP by ␣-secretase produces non-amyloidogenic peptides (3, 4). The ␥-secretase is an aspartyl protease complex composed of four core components, including presenilin (PS) 1 and PS2 (5). Early onset familial AD is linked to three genes, APP, PS1, and PS2 (5, 6), strongly suggesting that ␥-secretasedependent production of A␤ is a key factor in the pathogenesis of AD. Therefore, cellular factors that affect the ␥-secretase-dependent production of A␤ may be good targets for the development of drugs to prevent and treat AD.Both APP and PS-1 are transmembrane proteins, and their intracellular localization is controlled by secretory and endocytic pathways. These proteins are modified in the endoplasmic reticulum and trafficked to the cell surface through the transGolgi network (TGN). Then, they are internalized again and traf...

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Section: Contribution Of Co-internalization Of Ps-1 With the Ep 4 Recmentioning

confidence: 99%

Prostaglandin E2 Stimulates the Production of Amyloid-β Peptides through Internalization of the EP4 Receptor

Hoshino

Namba

Takehara

et al. 2009

Journal of Biological Chemistry

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“…In some cases, however, Ca 2+ and PKC are involved. 18 Since it is known that high enough intracellular calcium can uncouple gap junction channels 19 and that Ang II increases Ca 2+ i, 9 an additional mechanism for the action of losartan might be a possible decrease of the intracellular calcium concentration.…”

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%

Chronic blockade of angiotensin II AT1-receptors increased cell-to-cell communication, reduced fibrosis and improved impulse propagation in the failing heart

Mello

2006

J Renin Angiotensin Aldosterone Syst

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PaperAbstract I In nt tr ro od du uc ct ti io on n. . The influence of chronic administration of losartan on gap junction conductance (gj), conduction velocity and interstitial fibrosis was investigated in the failing heart of 4-month-old cardiomyopathic hamsters (TO-2).After two months of administration of losartan (25 mg/kg/day/po) the number of cell pairs showing very low values of gj (2-8 nS) was significantly reduced whereas the group of cell pairs with larger values of gj (18-45 nS) was significantly increased.The conduction velocity measured with intracellular microelectrodes in the wall of the left ventricle was enhanced from 38 + 2.3 cm/s (n=25) (control) to 49 + 2 cm/s (n=24) (p<0.05) after losartan administration. Moreover, the number of ventricular fibres showing non-propagated action potentials was significantly decreased (p<0.05) by losartan.The % area of interstitial fibrosis measured in the wall of the left ventricle was reduced from 22 + 1.4% (n=18) to 14 + 1.3% (n=18) (p<0.05) after losartan administration. C Co on nc cl lu us si io on n. . Chronic blockade of angiotensin II type 1 receptors increased gj in the failing heart. Moreover, the conduction velocity was enhanced in part by the increase of gj and in part by the decrease of interstitial fibrosis and structural remodelling. IntroductionEvidence has been presented that the activation of the plasma and cardiac renin angiotensin systems during the process of heart failure is largely responsible for the ventricular remodelling, changes in intercellular communication, impulse propagation and the generation of cardiac arrhythmias.

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“…Angiotensin II (Ang II) is a pleiotropic vasoactive peptide that binds to two specific receptor subtypes, AT 1 and AT 2 (7,8). Only a single AT 1 receptor gene is present in humans, but this receptor is encoded by at least two distinct genes (AT 1a and AT 1b ) in rodents, with 96% homology (9). AT 1 contributes to chronic diseases, such as hypertension, renal injury, atherosclerosis, and cardiac hypertrophy, by promoting cell growth, in-flammatory responses, and fibrosis.…”

mentioning

confidence: 99%

“…The Ang II signal transduction is mediated by G proteins, which activate several intracellular pathways, including Ca 2ϩ / protein kinase C (PKC), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase, and numerous tyrosine kinases, such as Src, Pyk2, p130Cas, and focal adhesion kinase (9,10). Ang II also activates nuclear transcription factors, including NF-B, activating protein-1, cyclic adenosine monophosphate response element binding protein, and nuclear factor of activated T cells (12,13,14).…”

mentioning

confidence: 99%

Suppressors of Cytokine Signaling Regulate Angiotensin II-Activated Janus Kinase-Signal Transducers and Activators of Transcription Pathway in Renal Cells

Hernández-Vargas¹,

López-Franco²,

Sanjuán³

et al. 2005

Journal of the American Society of Nephrology

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The angiotensin II type 1 receptor and receptor-associated proteins

Cited by 165 publications

References 113 publications

Prostaglandin E2 Stimulates the Production of Amyloid-β Peptides through Internalization of the EP4 Receptor

Prostaglandin E2 Stimulates the Production of Amyloid-β Peptides through Internalization of the EP4 Receptor

Chronic blockade of angiotensin II AT1-receptors increased cell-to-cell communication, reduced fibrosis and improved impulse propagation in the failing heart

Suppressors of Cytokine Signaling Regulate Angiotensin II-Activated Janus Kinase-Signal Transducers and Activators of Transcription Pathway in Renal Cells

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