Angiotensin II receptors in chromatin fragments generated by micrococcal nuclease

Ré, Richard N.; Vizard, Douglas L.; Brown, Jean; Bryan, Sara E.

doi:10.1016/0006-291x(84)91641-3

Cited by 102 publications

(44 citation statements)

References 10 publications

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“…Local angiotensin may also act on its prejunctional receptors on the noradrenergic nerve endings facilitating catecholamine release by a paracrine mechanism (17). It has been proposed that intracellular angiotensin II may have a direct intracrine effect on vascular myocyte function since specific saturable angiotensin II receptors have been detected in cellular nuclei (18) and a direct effect of angiotensin II on gene transcription has been reported (19). Since angiotensin II has recently been shown to stimulate growth of cultured smooth muscle cells as well as increase the expression of several protooncogenes and autocrine growth factors (20)(21)(22)(23), it may be postulated that this locally produced angiotensin II may be responsible, at least in part, for induction ofgenes responsible for smooth muscle cell hypertrophy or hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

Localization and differential regulation of angiotensinogen mRNA expression in the vessel wall.

Naftilan¹,

Zuo²,

Inglefinger³

et al. 1991

J. Clin. Invest.

128

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Recent data demonstrate the existence of a vascular renin angiotensin system. In this study we examine the localization of angiotensinogen mRNA in the blood vessel wall of two rat strains, the Wistar and Wistar Kyoto (WKY), as well as the regulation of vascular angiotensinogen mRNA expression by dietary sodium. Northern blot analysis and in situ hybridization histochemistry demonstrate that in both strains angiotensinogen mRNA is detected in the aortic medial smooth muscle layer as well as the periaortic fat. In WKY rats fed a 1.6% sodium diet, angiotensinogen mRNA concentration is 2.6-fold higher in the periaortic fat than in the smooth muscle, as analyzed by quantitative slot blot hybridization. Angiotensinogen mRNA expression in the medial smooth muscle layer is sodium regulated. After 5 d of a low (0.02%) sodium diet, smooth muscle angiotensinogen mRNA levels increase 3.2-fold (P < 0.005) as compared with the 1.6% sodium diet. In contrast, angiotensinogen mRNA level in the periaortic fat is not influenced by sodium diet. In summary, our data demonstrate regional (smooth muscle vs. periaortic fat) differential regulation of angiotensinogen mRNA levels in the blood vessel wall by sodium. This regional differential regulation by sodium may have important physiological implications. (J. Clin. Invest. 1991Invest. . 87:1300

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Section: Discussionmentioning

confidence: 99%

Localization and differential regulation of angiotensinogen mRNA expression in the vessel wall.

Naftilan¹,

Zuo²,

Inglefinger³

et al. 1991

J. Clin. Invest.

128

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“…As early as 1971, radiolabeled angiotensin II was reported to localize in the nuclei and mitochondria of cardiac myocytes after intracardiac injection in rats (19). In the 1980s, our group demonstrated specific, high-affinity receptors for angiotensin II on cell nuclei in association with chromatin; binding of angiotensin II to nuclei was shown to upregulate transcription (13)(14)(15)(16)(17). Later, Booz et al (2) and Tang et al (22) reported that nuclear angiotensin II receptors were similar to angiotensin type 1 (AT 1 ) receptors.…”

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confidence: 94%

Intracellular renin-angiotensin system: the tip of the intracrine physiology iceberg

Ré¹

2007

American Journal of Physiology-Heart and Circulatory Physiology

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IT IS AXIOMATIC THAT PEPTIDE hormones bind to cognate receptors on target cells, with the resultant generation of intracellular second messengers. Not as well known is the fact that a large and growing body of evidence indicates that extracellular signaling peptides, such as hormones and growth factors, also appear, in some cases, to operate in the interiors of cells after internalization or retention in the cells that synthesized them. This type of peptide action has been termed intracrine, and it is particularly relevant in the renin-angiotensin system (13,(15)(16)(17). In fact, angiotensin II was one of the first hormones for which such action was proposed.In this issue of the American Journal of Physiology-Heart and Circulatory Physiology, Singh and colleagues (21) have presented important data indicating the intracellular synthesis and nuclear trafficking of angiotensin II in neonatal cardiac myocytes stimulated by high glucose or isoproterenol. This study is important on several fronts. It represents the most recent fruit of a long progression of research and is best interpreted in that context. As early as 1971, radiolabeled angiotensin II was reported to localize in the nuclei and mitochondria of cardiac myocytes after intracardiac injection in rats (19). In the 1980s, our group demonstrated specific, high-affinity receptors for angiotensin II on cell nuclei in association with chromatin; binding of angiotensin II to nuclei was shown to upregulate transcription (13-17). Later, Booz et al. (2) and Tang et al. (22) reported that nuclear angiotensin II receptors were similar to angiotensin type 1 (AT 1 ) receptors. Still later, studies employing electron microscopy and immunohistochemistry demonstrated angiotensin II in association with euchromatin in normal animals (9). Eggena and colleagues (8) showed that treatment of isolated nuclei with angiotensin II led to the upregulation of renin and angiotensinogen transcription. At the same time, De Mello (7) and then Haller and Luft (11) showed that the introduction of angiotensin II into cells could have important effects on calcium currents; De Mello proposed an important role for intracellular angiotensin II in cardiac myocyte conductance and, by extension, in the pathogenesis of cardiac arrhythmias. Recent studies employing AT 1 receptor fluorescent fusion proteins have shown that angiotensin II binding to these receptors is associated with their internalization and trafficking to the nucleus (5, 6, 16). Indeed, our recent studies indicate that, in some cases, AT 1 receptor cleavage occurs with the receptor's cytoplasmic tail trafficking to the nucleus, a phenomenon seen with some tyrosine kinase receptors but not previously associated with G-coupled receptors (6).One issue raised by the studies described above is the site of synthesis of any angiotensin II that might be active in the intracellular space. That is, does the intracellular generation of angiotensin II occur, or must any intracellular angiotensin be internalized from the extracellular space? Th...

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“…[1][2][3][4] Re and colleagues 1 showed that isolated rat liver and spleen nuclei specifically bound 125 I-labeled Ang II with high affinity. In these studies, Ang II competed effectively for radiolabeled tracer whereas Ang I did so less effectively and neurotensin not at all.…”

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confidence: 99%

In Vitro Evidence for an Intracellular Site of Angiotensin Action

Cook

Zhou

Ré

2001

Circulation Research

Self Cite

132

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Abstract-To differentiate the relative effects of nuclear and cell surface angiotensin II (Ang II) receptors, we mutated the angiotensinogen cDNA by removing the signal sequence-encoding region to produce a nonsecreted form of angiotensinogen [Ang(ϪS)Exp]. Rat hepatoma cells (which produce renin and angiotensin-converting enzyme mRNAs) were stably transfected with Ang(ϪS)Exp/pSVL (or a corresponding control) expression plasmid, and mitotic indices were measured for stably transfected cell lines. Experimental clonal cell lines demonstrate an average of 33Ϯ4.4% (PϽ0.001) increase in percentage-labeled nuclei compared with control cell lines. The mitogenic effect is blocked by 10 Ϫ6 mol/L losartan and by 1 mol/L renin antisense phosphorothioate oligomers but not by 10 Ϫ6 mol/L candesartan. In addition, phenylarsine oxide, which blocks angiotensin receptor internalization, abolishes the losartan inhibitory effect, suggesting that after cell-surface receptor-mediated endocytosis, losartan blocks Ang II nuclear receptors. PDGF mRNA levels are elevated 2.2-fold in Ang(ϪS)Exp transfected cell lines; addition of anti-PDGF antibodies to the culture medium partially blocks the mitogenic effect of Ang(ϪS)Exp, while anti-Ang II antibodies have no effect. These results suggest that the Ang(ϪS)Exp growth effect is due, in part, to autocrine/paracrine stimulation by secreted PDGF after Ang II/Ang II receptor intracellular interactions. We further demonstrate that these cells produce the alternative renin transcript, renin 1A, which apparently lacks a signal sequence and is maintained intracellularly. Collectively, these studies of cultured cells suggest that some cell types may possess components of the renin-angiotensin system that permit intracellular processing of angiotensinogen to Ang II and that Ang II generated intracellularly may be mitogenic. Re and colleagues 1 showed that isolated rat liver and spleen nuclei specifically bound 125 I-labeled Ang II with high affinity. In these studies, Ang II competed effectively for radiolabeled tracer whereas Ang I did so less effectively and neurotensin not at all. Their studies extended earlier investigations that suggested that labeled Ang II localized to nuclear and mitochondrial regions of myocardial, brain, and smooth muscle cells. [5][6][7] Re and colleagues further demonstrated 125 I-Ang II binding to solubilized rat liver chromatin fragments, the existence of a discrete Ang II-binding nucleoprotein particle by deoxynucleoprotein gel electrophoresis, and direct effects of nuclear angiotensin on transcription. 2,8,9 In addition, Ang II immunoreactivity has been found associated specifically with euchromatin in cerebellum, liver, and adrenal tissue. 10 Erdmann and colleagues, 10 using immunogold staining, found Ang II immunoreactivity to be prominent in cerebellar neurons; the peptide was localized to nuclei and also to vesicle-like structures in cytoplasm. In some cell types such as endothelial and granule cells, the peptide was nearly exclusively present in the transcription...

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Angiotensin II receptors in chromatin fragments generated by micrococcal nuclease

Cited by 102 publications

References 10 publications

Localization and differential regulation of angiotensinogen mRNA expression in the vessel wall.

Localization and differential regulation of angiotensinogen mRNA expression in the vessel wall.

Intracellular renin-angiotensin system: the tip of the intracrine physiology iceberg

In Vitro Evidence for an Intracellular Site of Angiotensin Action

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