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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During human and rat pregnancy, several hemodynamic and endocrine processes are markedly modified. These include activation of the renin-angiotensin system (RAS) and increase of plasma aldosterone. However, the rise of plasma aldosterone is greater than expected from the elevation of RAS activity. Gestational alterations in angiotensin II receptors (AT receptor) in the adrenal could explain this apparent hyperaldosteronism. This study was conducted to determine differences between AT receptor subtypes in the adrenal glands of non-pregnant and pregnant (22 days) rats. Using plasma membrane preparations from adrenal glomerulosa and medulla, we determined receptor density and affinity with 125I-angiotensin II (ANG II); the AT receptor subtypes were assessed by displacement of 125I-ANG II binding with subtype-specific antagonists (DuP753 and PD123319). In zona glomerulosa of non-pregnant and pregnant rats, AT1 receptors predominated (approximately 80%) with no statistical difference in receptor density (Bmax) and affinity (Kd) and the ratio of receptor subtypes between the two groups of rats. In adrenal medulla of both groups of rats, the major portion of 125I-ANG II binding (60-70%) was displaced by the AT2 receptor antagonist, PD123319. Neither Bmax nor Kd differed in this tissue during gestation. The results for AT1 receptor density were confirmed by Western blot. Northern blot analysis showed that AT1 mRNA level in the adrenal is not modified by gestation. These results indicate that the number, the affinity and the transcription of the AT1 receptor in the adrenal are not altered during pregnancy, indicating that the rise in aldosterone secretion during pregnancy could not be explained by increase of AT1 receptors in the zona glomerulosa, or modification of AT1/AT2 ratio.
Mol Cell Endocrinol 1995 Oct 30
PMID:Angiotensin II receptor subtypes in the adrenals of pregnant rats. 867 42

The intrarenal renin-angiotensin system (RAS) contributes to the increased renal vascular resistance and reactivity observed in spontaneously hypertensive rats (SHR) and to the pathogenesis of high blood pressure (BP). Thus, we decided to characterize angiotensin II (ANG II) receptors in the renal arteries and glomeruli of 16-week-old SHR and their age-matched, normotensive Wistar-Kyoto (WKY) controls. SHR had significantly higher BP (153 +/- 4 v 96 +/- 10 mmHg) and heart weight (440 +/- 5 v 327 +/- 4 g/100 g body weight) than WKY rats. There was no difference in plasma renin activity between strains. Radioligand binding assays using non-peptide antagonists for AT1 (losartan) and AT2 (PD 123319) showed that renal preglomerular microvessels and glomeruli expressed a single receptor population (AT1) for ANG II. AT1 density tended to be lower in glomeruli of SHR compared to WKY (377 +/- 45 v 555 +/- 74 fmol/mg protein), but was significantly higher in preglomerular vessels (93 +/- 7 v 57 +/- 1 fmol/mg protein). No difference in receptor affinity was found in either preparation. Isolated kidney perfusion revealed that at low flow (3-10 ml/min), perfusion pressure was similar in both strains; however, at higher flow levels, SHR showed higher reactivity and less compliance than their controls. In addition, SHR presented a higher renal vascular reactivity to ANG II (but not to arterenol) than WKY rats. Thus, upregulation of ANG II receptors in the renal vasculature may mediate the hyperreactivity to ANG II observed in SHR kidney.
J Mol Cell Cardiol 1996 Feb
PMID:Characterization and hemodynamic implications of renal vascular angiotensin II receptors in SHR. 872 67

The plasma and cardiac renin-angiotensin systems may be activated after myocardial infarction. The myocardium may therefore be exposed to increased concentrations of angiotension II, which may contribute to myocardial injury. The purpose of this study was to identify the potential sites of action of angiotensin II in the infarcted heart. Myocardial infarction was induced in rats by left coronary artery ligation, and the hearts were removed for study after 18 h, 7 days, or 8 months. The regional ventricular angiotensin II receptor density was assessed by [125I](Sar1,Ile8)angiotensin II binding and quantitative autoradiography. The [125I](Sar1,Ile8)angiotensin II binding was unchanged at 18 h, but was increased at 7 days in the infarcted region of the left ventricle (73.2 +/- 3.2 amol/mm2, mean +/- S.E.M.) compared with the non-infarcted region (1.6 +/- 0.2 amol/mm2, P < 0.0001) and with the left ventricular myocardium of sham-operated control animals (1.3 +/- 0.1 amol/mm2, P < 0.0001). The increased [125I](Sar1,Ile8)angiotensin II binding density was still present, but diminished, at 8 months after coronary ligation (49.0 +/- 5.7 amol/mm2, P < 0.0001 v control, P = 0.0058 v 7-day infarcts). The increased binding of [125I](Sar1,Ile8)angiotensin II was antagonised by losartan, an AT1 receptor antagonist, but not by an AT2 receptor antagonist. Microautoradiography of [125I](Sar1,Ile8) angiotensin II, and assessment of collagen deposition using picrosirius staining and immunostaining demonstrated that the regional increase in AT1 receptor density in the infarcted region of myocardium was associated with fibroblast infiltration and collagen deposition. The infarct scar and the cardiac fibroblasts within it express high levels of angiotension II receptors and therefore represent potential targets for the actions of angiotensin II after myocardial infarction.
J Mol Cell Cardiol 1996 Feb
PMID:Regional changes in angiotensin II receptor density after experimental myocardial infarction. 872 73

Angiotensin II has been demonstrated to be involved in the regulation of cellular growth of several tissues in response to developmental, physiological, and pathophysiological processes. Angiotensin II has been implicated in the developmental growth of the left ventricle in the neonate and remodeling of the heart following chronic hypertension and myocardial infarction. The inhibition of DNA synthesis and collagen deposition in myocardial interstitium following myocardial infarction by angiotensin converting enzyme inhibitor, suggests that angiotensin II mediates interstitial and perivascular fibrobrosis by preventing fibroblast proliferation. In the past, little attention was focused on the identity and functional roles of cardiac fibroblasts. Recent in vitro studies utilizing cultured cardiac fibroblasts demonstrate that angiotensin II, acting via the AT1 receptor, initiates intracellular signalling pathways in common with those of peptide growth factors. Below, we describe growth-related aspects of cardiac fibroblasts with respect to angiotensin II receptors, conventional and novel signal transduction systems, secretion of extracellular matrix proteins and growth factors, and localization of renin-angiotensin system components.
Mol Cell Biochem
PMID:Angiotensin II signalling pathways in cardiac fibroblasts: conventional versus novel mechanisms in mediating cardiac growth and function. 873 24

In eukaryotic cells, checkpoint genes cause arrest of cell division when DNA is damaged or when DNA replication is blocked. In this study of budding yeast checkpoint genes, we identify and characterize another role for these checkpoint genes after DNA damage-transcriptional induction of genes. We found that three checkpoint genes (of six genes tested) have strong and distinct roles in transcriptional induction in four distinct pathways of regulation (each defined by induction of specific genes). MEC1 mediates the response in three transcriptional pathways, RAD53 mediates two of these pathways, and RAD17 mediates but a single pathway. The three other checkpoint genes (including RAD9) have small (twofold) but significant roles in transcriptional induction in all pathways. One of the pathways that we identify here leads to induction of MEC1 and RAD53 checkpoint genes themselves. This suggests a positive feedback circuit that may increase the cell's ability to respond to DNA damage. We make two primary conclusions from these studies. First, MEC1 appears to be the key regulator because it is required for all responses (both transcriptional and cell cycle arrest), while other genes serve only a subset of these responses. Second, the two types of responses, transcriptional induction and cell cycle arrest, appear distinct because both require MEC1 yet only cell cycle arrest requires RAD9. These and other results were used to formulate a working model of checkpoint gene function that accounts for roles of different checkpoint genes in different responses and after different types of damage. The conclusion that the yeast MEC1 gene is a key regulator also has implications for the role of a putative human homologue, the ATM gene.
Mol Biol Cell 1996 May
PMID:Distinct roles of yeast MEC and RAD checkpoint genes in transcriptional induction after DNA damage and implications for function. 874 45

The actions of angiotensin II in the cardiovascular system are transmitted by two known and possibly some unknown angiotensin receptor types. AT1 and AT2 both correspond to G-protein-coupled receptors with seven hydrophobic transmembrane domains, several N-glycosylation sites and a potential G-protein binding site. Cloning of coding regions and promoter sequences contributed to the understanding of receptor protein function and regulation. Angiotensin receptors with atypical binding properties for the known AT1- and AT2-specific ligands are expressed on human cardiac fibroblasts and in the human ulcrus. In several animal models, receptors with high affinity for angiotensin (1-7) have been described. AT1 stimulation is mediated by the generation of phospholipid-derived second messengers, activation of protein kinase C, the MAPkinase pathway and of immediate early genes. Recently, phosphorylation and dephosphorylation of tyrosine kinases have been associated with AT1- and AT2-mediated signal transduction. ATR are regulated by phosphorylation, internalization, modification of transcription rate and mRNA stability. Regulation is highly cell and organ specific and includes upregulation of ATR in some pathophysiological situations where the renin angiotensin system is activated. Whereas the function of AT1 in the cardiovascular system is relatively well established, there is little information regarding the role of AT2. Recent hypotheses suggest an antagonism between AT1 and AT2 at the signal transduction and the functional level. Transgenic animal models, particularly with targeted disruption of the AT1 and AT2 genes, suggest the contribution of both genes to blood pressure regulation. Genetic polymorphisms have been described in the AT1 and AT2 gene or neighbored regions and are used to analyze the association between gene defects and cardiovascular diseases. AT1 antagonists are now being introduced into the treatment of hypertension and potentially heart failure, and more interesting pharmacological developments are expected from the ongoing basic studies.
J Mol Med (Berl) 1996 May
PMID:Molecular biology of angiotensin receptors and their role in human cardiovascular disease. 877 61

Ataxia telangiectasia is a recessive disorder in which patients show a progressive cerebellar degeneration leading to ataxia, abnormal eye movements and deterioration of speech. Other features include ocular telangiectasia, high serum AFP levels, immunodeficiency, growth retardation and an increased predisposition to some tumours, particularly T cell leukaemia and lymphoma. We report the 1348 amino acid sequence of the N-terminal half of the A-T gene product which, together with the previously published C-terminal half, completes the sequence of the A-T protein. No homologies with other genes have been found within the N-terminal half of the A-T protein. We have also identified six mutations affecting the N-terminal half of the protein. One of these mutations was found to be associated with a haplotype that is common to four apparently unrelated families of Irish descent. All the patients so far examined for both A-T alleles were shown to be compound heterozygotes. None of these mutations affected a putative promoter region which may direct divergent transcription of both the A-T gene and a novel gene E14. The ability to recognise mutations across the entire coding sequence of the A-T gene provides a practical advantage to A-T families since a DNA based prenatal diagnosis will be possible in families where the mutations are identified irrespective of the level of radiosensitivity in these families.
Hum Mol Genet 1996 Jan
PMID:Mutations revealed by sequencing the 5' half of the gene for ataxia telangiectasia. 878 52

The AT hook is an AT-rich DNA-binding domain that occurs three times in mammalian high-mobility-group I/Y chromosomal proteins and has recently also been identified in DNA-binding proteins from plants. We unexpectedly isolated three rice cDNA clones encoding AT hook-containing proteins in an attempt to isolate homeobox cDNA clones by south-western screening of an expression library with known binding sites for Arabidopsis and animal homeodomain proteins. One of these clones (Os-PF1) has previously been identified due to the binding of its encoded protein to PE1, a cis-acting element from the oat phytochrome promoter. The other two clones represent newly described cDNA clones, designated Os-AT1 and Os-AT2. The Os-AT1 and Os-AT2 proteins were found to have the same specificities as Os-PF1 with respect to in vitro binding of wild-type and mutant PE1 versions. However, all three proteins appeared to bind much stronger in south-western assays to two of the rather AT-rich sequences used in our screening than to the PE1 element. In none of the AT hook proteins clear homologies to transcriptional activation domains could be identified, but the N-terminal regions of Os-AT1 and Os-PF1 were found to show similarity to histone H1 chromosomal proteins. Given their structural characteristics it is conceivable that the rice AT hook proteins bind to gene promoter regions as accessory proteins that may alter the accessibility of chromatin to other nuclear factors. Their predominant expression in young and meristematic tissues suggests that the presence of the AT hook proteins may affect the expression of genes that determine the differentiation status of cells.
Plant Mol Biol 1996 Jun
PMID:Novel members of a family of AT hook-containing DNA-binding proteins from rice are identified through their in vitro interaction with consensus target sites of plant and animal homeodomain proteins. 879 Feb 93

To understand the molecular mechanism by which the angiotensin II (AII) type 1 receptor (AT1 receptor) transduces its biological signal, we examined the role of various signaling molecules involved in AT1 receptor signaling in Chinese hamster ovary cells stably transfected with the AT1 receptor. AT1 receptor-transfected cells responded to AII treatment by inhibiting adenylyl cyclase, increasing the intracellular Ca2+ concentration, and activating protein kinase C (PKC) alpha and PKC epsilon. AII also activated the c-fos gene and mitogen-activated protein (MAP) kinases. The activation of PKC, the c-fos gene, and MAP kinases was blocked by inhibition of PKC induced by pretreatment with 12-O-tetradecanoylphorbol-13-acetate but not by pretreatment with pertussis toxin, suggesting that PKC couples to the activation of the the c-fos gene and MAP kinases. In addition, AII activated Raf-1 and MAP kinase kinase in a PKC-dependent manner. A dominant negative mutant of Ras had no effect on AII-induced MAP kinase or c-fos gene activation. Thus, the AT1 receptor signals through Raf-1 and its downstream signaling molecules by a PKC-dependent mechanism that does not involve Ras activation.
Mol Pharmacol 1996 Sep
PMID:Angiotensin II type 1 receptor signals through Raf-1 by a protein kinase C-dependent, Ras-independent mechanism. 879 90

Two genes that are highly expressed in the tomato shoot apex have been cloned by differential hybridization. One of the deduced polypeptides (AT1) shows significant similarities to class II proteinase inhibitors, while the other (AT2) displays similarities to defensins. Transcripts of both genes are also detectable in the developing flower and are present only in minor amounts in other tissues tested. In situ hybridization analysis revealed that both genes are expressed in non-overlapping subsets of cells in the shoot apex, as well as in the developing flower. The potential use of these genes as markers for certain cell types and the possible biological function of the encoded proteins are discussed.
Mol Gen Genet 1996 Aug 27
PMID:Expression of genes for a defensin and a proteinase inhibitor in specific areas of the shoot apex and the developing flower in tomato. 880 87


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