Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “RRM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2004

Structure and RNA interactions of the N-terminal RRM domains of PTB.

The polypyrimidine tract binding protein (PTB) is an important regulator of alternative splicing that also affects mRNA localization, stabilization, polyadenylation, and translation. NMR structural analysis of the N-terminal half of PTB (residues 55-301) shows a canonical structure for RRM1 but reveals novel extensions to the beta strands and C terminus of RRM2 that significantly modify the beta sheet RNA binding surface. Although PTB contains four RNA recognition motifs (RRMs), it is widely held that only RRMs 3 and 4 are involved in RNA binding and that RRM2 mediates homodimerization. However, we show here not only that the RRMs 1 and 2 contribute substantially to RNA binding but also that full-length PTB is monomeric, with an elongated structure determined by X-ray solution scattering that is consistent with a linear arrangement of the constituent RRMs. These new insights into the structure and RNA binding properties of PTB suggest revised models of its mechanism of action.

Amino Acid Sequence↗
PubMed2001

Identification of two Entamoeba histolytica sequence-specific URE4 enhancer-binding proteins with homology to the RNA-binding motif RRM.

To study transcriptional regulation in the lower branching eukaryote Entamoeba histolytica, we have identified two sequence-specific DNA-binding proteins that recognize the upstream regulatory element URE4, an enhancer that regulates expression of the Gal/GalNAc lectin heavy subunit gene hgl5. A chromatographic purification of E. histolytica nuclear extracts by gel filtration, cation exchange, and sequence-specific DNA affinity chromatography led to a 700-fold increase in URE4 binding activity and the appearance of two dominant protein species with molecular masses of 28 and 18 kDa. These proteins, termed E. histolytica enhancer-binding proteins 1 and 2 (EhEBP1 and EhEBP2), were sequenced by tandem mass spectroscopy and their corresponding cDNA clones identified. Recombinant EhEBP1 and EhEBP2 were able to bind double-stranded oligonucleotides bearing the URE4 motif in a sequence-specific manner, and antibodies raised against EhEBP1 were able to interfere with the formation of URE4-protein complexes in crude nuclear extracts. Overexpression of EhEBP1 in E. histolytica trophozoites resulted in a 7-fold drop in promoter activity in transiently transfected reporter gene constructs when the URE4 motif was present, confirming its ability to specifically recognize the URE4 motif and suggesting that additional cofactors may be required for transcriptional activation by URE4. Further characterization and identification of binding partners for EhEBP1 and EhEBP2, the first proteins with demonstrated sequence-specific DNA binding activity to be identified in E. histolytica, should provide new insights into transcriptional regulation in this protozoan parasite.

Amino Acid Sequence↗
PubMed1997

Crystallization and preliminary X-ray diffraction studies of UP1, the two-RRM domain of hnRNP A1.

The N-terminal domain of hnRNP A1 protein, termed UP1, comprises two tandem RNA-recognition motifs, both of which are necessary for efficient RNA binding and for the alternative splicing activity of hnRNP A1. Recombinant human UPI expressed in E. coli has been crystallized in space group P2(1) with unit-cell dimensions a = 37.94, b = 43.98, c = 55.64 A and beta = 93.9 degrees. The unit-cell volume is consistent with one UP1 molecule per asymmetric unit and a calculated 49% solvent content. The crystal diffraction limit is higher than 1.3 A, and a data set to 2.0 A has been collected. Diffraction data from one platinum and two mercury derivatives have also been collected.

Journal Article↗
PubMed2000

Mechanism of antihypertensive effect of dietary potassium in experimental volume expanded hypertension in rats.

Dietary potassium supplementation lowers blood pressure (BP) and attenuates complications in hypertensive subjects, particularly those with the low renin volume expanded (LRVE) variety. We and others have shown that the plasma level of a digitalis like substance (DLS) is elevated in this type of hypertension. We therefore, examined the effect of increases in dietary potassium on the plasma level of endogenous DLS, myocardial and renal Na+, K+-ATPase (NKA) activities, BP, and renal excretory function in reduced renal mass (RRM)-salt hypertension in the rat, a classical model of LRVE hypertension. 70% RRM rats were divided in 4 groups, namely those consuming: 1) a sodium free and normal potassium (1.3% as KCl) diet (RRM-0 Na), 2) a normal sodium and normal potassium diet (RRM-NaK), 3) a normal sodium and high potassium (2 X normal) diet (RRM-Na2K), and 4) a normal sodium and 4 times normal potassium diet (RRM-Na4K). At the end of 4 weeks of dietary treatment, direct BP was recorded, plasma level of DLS determined by bioassay and with a radioimmunoassay for digoxin (DIF) and myocardial and renal NKA activities were measured. As expected, compared to RRM-0Na rats, RRM-NaK rats developed hypertension. BP increased significantly less in RRM-Na2K, whereas BP did not increase in RRM-Na4K rats. Hypertension in RRM-NaK rats was associated with an increase in plasma DLS and DIF and decrease in renal and myocardial NKA activities. DLS was increased (DIF was not changed) and myocardial NKA also decreased in rats consuming double potassium. However, quadrupling potassium in the diet (RRM-Na4K) normalized DLS and DIF and increased myocardial and renal NKA activities, compared to RRM-0Na rats. Also compared to RRM-0Na, water consumption, urinary volume excretion, sodium, and potassium increased in the other 3 groups, more so in RRM-Na4K rats. These data show that quadrupling the potassium in the diet prevents the BP increase in RRM rats and this is associated with diuresis/natriuresis and normalization of DLS, perhaps because the diuresis/natriuresis normalizes blood volume.

Animals↗
PubMed1996

Regulation of ANG II receptor in hypertension: role of ANG II.

To investigate the role of angiotensin II (ANG II) in the development of hypertension induced by reduced renal mass (RRM) and the gene expression of ANG II type 1 (AT1) receptors in the remnant renal tissue, four groups of rats were given 1% NaCl in water and subjected to RRM, RRM+ ramipril, RRM+ losartan, or sham surgery (control). Tail-cuff systolic blood pressure was significantly higher in RRM rats than in the other three groups. Northern blot showed that AT1 gene expression was significantly decreased in RRM, RRM + ramipril, or RRM + losartan vs. control. There was no significant difference among the three RRM groups. Renal transforming growth factor-beta 1 (TGF-beta 1) mRNA levels were increased threefold (P < 0.05) in RRM, RRM+ ramipril, and RRM+ losartan vs. control. There was no significant difference among the three RRM groups. We conclude that the development of RRM hypertension is ANG II dependent but not mediated by AT1 gene expression. RRM downregulates AT1 mRNA and upregulates TGF-beta 1 mRNA in the remnant renal tissue, regardless of blood pressure or plasma levels of ANG II, suggesting that these gene responses are triggered by an effect of local injury.

Angiotensin II↗
PubMed1997

Distinct mechanisms of modulation of angiotensin II type I receptor gene expression in heart and aorta.

The purpose of the present study was to test the hypothesis that hypertension induced by reduced renal mass (RRM) upregulates gene expression of the type 1 angiotensin II (Ang II) receptor (AT1) in the thoracic aorta and heart through an Ang II-dependent mechanism. Three groups of rats were given 1% NaCl water and subjected to RRM, RRM plus captopril (RRM+Cap, 30 mg/kg per day), or sham surgery. Tail-cuff systolic blood pressure was significantly elevated in RRM and RRM+Cap rats compared with sham-operated rats. The ratios of the medial wall area of the thoracic aorta and heart weight to body weight were significantly elevated in RRM and RRM+Cap rats compared with sham-operated rats. Northern blot analysis indicated that the ratio of AT1 to GAPDH mRNA in the aorta was significantly higher in RRM (1.85 +/- 0.52) compared with sham-operated (0.21 +/- 0.04) and RRM+Cap (0.55 +/- 0.20) rats. In contrast, the ratio of AT1 to GAPDH mRNA in the heart was significantly increased in both RRM (1.09 +/- 0.23) and RRM+Cap (1.00 +/- 0.09) compared with sham-operated (0.34 +/- 0.06) rats. Thus, RRM hypertension upregulates AT1 mRNA expression in both the hypertrophied aorta and heart. Captopril treatment without altering blood pressure in RRM rats prevents the increase in AT1 mRNA in the aorta but not the heart. These results suggest that different tissue-specific mechanisms of AT1 gene regulation exist; ie, in aorta, an Ang II-or kinin-dependent mechanism is operant, whereas in heart, RRM-induced upregulation of AT1 mRNA may be pressure dependent.

Angiotensin Receptor Antagonists↗
PubMed1999

Reciprocal role of the AT1 receptor in modulating renal and neuronal AT1 mRNA expression.

This study was designed to explore the mechanisms mediating the expression of the type 1 angiotensin II (AngII) receptor (AT1) in neuronal and renal tissues. Four groups of rats were given 1% NaCl in water and subjected to the renal reduced mass protocol (RRM), RRM + ramipril (Ram, 10 mg/kg per d), RRM + candesartan (Can, 10 mg/kg per d), or sham surgery. After 12 d, mean arterial pressure (MAP) was significantly higher in RRM rats than in RRM + Ram, RRM + Can, and sham-operated rats. Northern blot analysis showed that renal AT1 receptor mRNA levels (AT1 mRNA/18 rRNA) were significantly decreased in RRM (1.08+/-0.05) and RRM + Ram (0.82+/-0.02) compared with sham-operated rats (1.38+/-0.06) and that candesartan treatment caused a further decrease in renal AT1 mRNA content (0.73+/-0.07) compared with RRM. In contrast, dorsal root ganglia AT1 receptor mRNA content was significantly decreased in RRM (0.52+/-0.06) compared with sham-operated rats (1.18+/-0.07), and this decrease was abolished by ramipril (1.40+/-0.13) and candesartan treatment (1.56+/-0.11). RIA showed that levels (ng/mg protein) of calcitonin gene-related peptide (CGRP) in the dorsal root ganglia were significantly increased in RRM (1.60+/-0.11) but not in RRM + Ram (1.14+/-0.20) and RRM + Can (1.18+/-0.09), compared with sham-operated rats (0.94+/-0.05). Thus, RRM-induced downregulation of neuronal AT1 mRNA expression is mediated by AngII activation of the AT1 receptor, whereas an AT1-independent mechanism is operant in mediating renal AT1 gene expression. Furthermore, the inverse relationship between neuronal AT1 expression and CGRP content indicates that activation of the neuronal AT1 receptor inhibits CGRP synthesis in the dorsal root ganglia. The functional implications of these findings are discussed.

Angiotensin I↗
PubMed1992

A consistent model of insulin-dependent diabetes mellitus hypertension.

Hypertension is frequently seen in insulin-dependent diabetes mellitus (IDDM), but the mechanism of the hypertension is unknown. An animal model of IDDM hypertension could be helpful in determining the mechanism, but experimental IDDM has been infrequently and irregularly associated with hypertension. In an attempt to develop a consistent model of IDDM hypertension, we superimposed streptozotocin (STZ)-induced IDDM on surgical reduction of renal mass (RRM) in Wistar rats. Seven groups of rats were studied: 1) 60% RRM receiving 65 mg/kg body weight (BW) STZ; 2) 60% RRM receiving 40 mg/kg BW STZ; 3) 25% RRM receiving 65 mg/kg BW STZ; 4) two kidney normal rats receiving 65 mg/kg BW STZ; 5) 60% RRM receiving vehicle (control for group 1); 6) 60% RRM receiving vehicle (control for group 2); and 7) 25% RRM receiving vehicle. STZ produced diabetes and hypertension within 1 to 2 weeks in all three groups of RRM rats but blood pressure was unaffected by 60% or 25% RRM alone. STZ alone had no effect on blood pressure until the 5th week when the blood pressure increased slightly. Progressive weight loss resulted from 65 mg/kg BW STZ combined with 60% RRM; the animals had to be terminated after 5 weeks. In only 60% of animals with 40 mg/kg BW STZ plus 60% RRM was IDDM produced. On the other hand, 65 mg/kg BW STZ in rats with 25% RRM regularly produced IDDM and hypertension without excessive loss of body weight. In these rats, albuminuria developed in 2 weeks. Extracellular fluid volume was elevated and plasma renin activity was depressed. The animals were healthy and hypertensive when killed at the 13th week. We suggest that the 25% RRM rat receiving 65 mg/kg BW STZ is a consistent model of IDDM hypertension, which may be useful in probing the mechanism of this type of hypertension.

Albuminuria↗
PubMed1989

Plasma atrial natriuretic peptide in conscious rats with reduced renal mass.

The effect of salt intake and reduction of renal mass (RRM) on plasma immunoreactive atrial natriuretic peptide (iANP) levels in conscious rats was studied. Rats were divided into RRM and sham-operated groups, and then further subdivided into groups infused with 1 or 6 mEq of sodium per day. Plasma urea nitrogen increased in the groups with RRM. Plasma sodium, sodium balance, and heart rate did not differ between the sham and RRM groups. Rats with RRM maintained on 1 mEq of sodium per day did not have an elevation of water intake, arterial pressure, or plasma iANP. Rats with RRM maintained on 6 mEq of sodium per day had significantly (P less than 0.05) elevated water intake, arterial pressure, and plasma iANP. Arterial pressure and plasma iANP were correlated (r = 0.800) for rats with RRM on either 1 or 6 mEq of sodium per day. Increased plasma iANP in the RRM group on 6 mEq per day was not caused by either RRM or high sodium alone; it was an effect of RRM plus high salt intake. The increase in plasma iANP in the RRM group may be caused by the increase in arterial pressure, possibly due to an increase in extracellular fluid volume. ANP may not be responsible for the sustained increase in fractional sodium excretion observed in RRM.

Animals↗
PubMed1994

Role of ouabainlike compound in rats with reduced renal mass-saline hypertension.

Ouabainlike compound (OLC) has recently been identified as a likely mammalian endogenous digitalis-like factor (EDLF) from human plasma. In this study, plasma levels of OLC were determined to assess the role of OLC in a model known as volume-expanded, reduced renal mass (RRM)-saline (S) hypertension in rats with use of a newly developed radioimmunoassay for ouabain. In the first experiment, at 3 wk after subtotal nephrectomy and drinking 1% saline solution, sysolic blood pressure (SBP) of 18 rats with reduced renal mass (RRM-S rats) was significantly higher than in 17 sham-operated saline-drinking control (C-S) rats [154 +/- 4 (SE) vs. 132 +/- 2 mmHg; P < 0.01]. Plasma OLC levels were 355 +/- 68 pmol/l in RRM-S rats, sevenfold higher than in C-S rats (54 +/- 4 pmol/l; P < 0.01). In the second experiment, we measured plasma OLC levels of 10 RRM-S, 12 sham-operated control (C), and 10 subtotally nephrectomized rats drinking distilled water (RRM rats). Concomitant with a marked increase in blood pressure (203 +/- 5 mmHg), RRM-S rats showed significantly higher plasma OLC levels compared with C and RRM rats (RRM-S 114 +/- 24, C 47 +/- 11, and RRM 52 +/- 9 pmol/l; P < 0.05). In both experiments, plasma OLC levels correlated significantly with SBP (P < 0.05). These findings suggest that plasma OLC shows a similar behavior to that of EDLFs or Na(+)-K(+)-adenosinetriphosphatase inhibitors reported in previous publications and may play a role in hypertensive mechanisms in rats with RRM and excess Na intake.

Animals↗
PubMed1995

The role of renal natriuretic depressor systems on hypertensive mechanisms in reduced renal mass hypertensive rats.

The pathophysiological role of renal natriuretic depressor systems and endogenous digitalis like factor (EDLF) on blood pressure (BP) elevation was studied in reduced renal mass rats (RRM) with saline loading for a model of volume dependent hypertension. Fifty-four male Sprague-Dawley rats were operated on to remove varying proportions of their kidney mass (5/6 RRM, n = 13; 4/6 RRM, n = 16; 3/6 RRM, n = 12) or sham operated (control, n = 13). They were given 1% saline to drink for 4 weeks. BP was elevated significantly at the 1st week in 5/6 RRM and continued to increase until the 4th week, but this was not seen in the other 3 groups. Urine volume (UV) and urinary sodium excretion (UNaV) increased after saline loading in all groups. Urinary kallikrein excretion was significantly lower in order of the 5/6, 4/6 and 3/6 RRM at the basal state and after saline loading. A significant negative correlation was observed between urinary kallikrein and BP. Urinary PGE2 was increased in each RRM in order of the 5/6, 4/6 and 3/6 RRM groups. A significant positive correlation was observed between urinary PGE2 and BP, UV or UNaV. The basal urinary DA excretion was significantly lower in 3 RRMs than in the control. After saline drinking, urinary DA increased in 3 RRMs, while differences disappeared in the control and RRMs. Urinary EDLF increased immediately after the initiation of saline loading in all groups, except the control group, and returned to the basal level 2 weeks later in 3/6 and 4/6 RRM. Only in 5/6 RRM, the urinary EDLF remained higher than the basal level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression.

The RNA recognition motif (RRM), also known as RNA-binding domain (RBD) or ribonucleoprotein domain (RNP) is one of the most abundant protein domains in eukaryotes. Based on the comparison of more than 40 structures including 15 complexes (RRM-RNA or RRM-protein), we reviewed the structure-function relationships of this domain. We identified and classified the different structural elements of the RRM that are important for binding a multitude of RNA sequences and proteins. Common structural aspects were extracted that allowed us to define a structural leitmotif of the RRM-nucleic acid interface with its variations. Outside of the two conserved RNP motifs that lie in the center of the RRM beta-sheet, the two external beta-strands, the loops, the C- and N-termini, or even a second RRM domain allow high RNA-binding affinity and specific recognition. Protein-RRM interactions that have been found in several structures reinforce the notion of an extreme structural versatility of this domain supporting the numerous biological functions of the RRM-containing proteins.

Amino Acid Sequence↗
PubMed1993

Long-term ouabain administration produces hypertension in rats.

Ouabain has recently been identified as an endogenous Na(+)-K+ pump inhibitor. We administered ouabain chronically to normotensive rats with varying degrees of reduced renal mass (RRM) and to normal two-kidney rats to see whether hypertension could be produced. Normal male Wistar rats and rats with 25%, 60%, and 70% RRM received ouabain (13.9 micrograms/kg per day IP) in normal saline for 4 weeks followed by ouabain (27.8 micrograms/kg per day IP) for 3 to 4 more weeks. Respective control animals received vehicle only. Blood pressure was recorded weekly by tail plethysmography. Animals received tap water and standard rat chow, except for 70% RRM rats, which received distilled water and sodium-free chow. After 6 to 8 weeks of treatment, with rats under thiobutabarbital anesthesia, direct blood pressure was determined. Plasma, tissue, and urinary ouabain levels were measured with a specific radioimmunoassay. Animals receiving ouabain developed significant increases in mean blood pressure compared with control animals (70% RRM, 147 +/- 4 vs 116 +/- 4 mm Hg; 60% RRM, 140 +/- 4 vs 107 +/- 3 mm Hg; 25% RRM, 131 +/- 5 vs 100 +/- 2 mm Hg; no RRM, 116 +/- 4 vs 98 +/- 5 mm Hg). Plasma ouabain levels measured 24 hours after the last ouabain dose were not different in animals receiving ouabain vs those receiving vehicle. However, kidney tissue ouabain levels were significantly greater (6.39 +/- 1.17 vs 2.36 +/- 0.52 micrograms/kg, P < .05) in animals receiving ouabain. In conclusion, ouabain, given chronically, is associated with the development of hypertension in RRM rats as well as in normal rats. Blood pressure was greater in animals with greater degrees of RRM for a given ouabain dose.

Animals↗
PubMed2003

Genetic evaluation of growth in nellore cattle by multiple-trait and random regression models.

The objective of this study was to identify issues in genetic evaluation of beef cattle for growth by a random regression model (RRM). Genetic evaluation data included 2,946,847 records of up to nine sequential weights of 812,393 Nellore cattle measured at ages ranging from birth to 733 d. Models considered were a five-trait multiple-trait model (MTM) and a cubic RRM. The MTM included the effects of contemporary group, age of dam class, additive direct, additive maternal, and maternal permanent environment. Both additive effects were assumed correlated. The RRM included the same effects as MTM, with the addition of permanent and random error effects. The purpose of the random error effect, which was in addition to a residual effect with constant variance, was to model heterogeneous residual variances. All effects in RRM were modeled as cubic Legendre polynomials. Expected progeny differences (EPD) were obtained iteratively using a preconditioned conjugate gradient algorithm. Numerically accurate solutions with RRM were not obtained until the random regressions were orthogonalized. Computing requirements of RRM were reduced by more than 50%, without affecting the accuracy by removing regressions corresponding to very low eigen-values and by replacing the random error effects with weights. Afterward, the correlations between EPD from RRM and from MTM for EPD on selected weights were between 0.84 and 0.89. For sires with at least 50 progeny, these correlations increased to 0.92 to 0.97. Low correlations were caused by differences in parameters. The RRM applied to growth i s prone to numerical problems. Estimates of EPD with RRM may be more accurate than those with MTM only if accurate parameters are applied.

Age Factors↗
PubMed1998

Gender-specific protection from microvessel rarefaction in female hypertensive rats.

Epidemiologic studies reveal that women have a significantly lower age-adjusted morbidity and mortality from cardiovascular disease than men, suggesting that gender is a cardiovascular disease risk factor. The mechanism of the "gender protection" is unknown. In this study, we investigated the microvascular remodeling in reduced renal mass plus a high salt (4.0% NaCl) diet model of hypertension (RRM + HS). We hypothesized that women would be protected from the increase in blood pressure and from the microvascular rarefaction associated with RRM + HS hypertension. Studies were designed to determine whether female rats were less susceptible to changes in microvessel density during RRM + HS. Microvessel density was measured in male and female low salt (0.4% LS) sham-operated controls (Sham + LS) and after 3 days or 4 weeks of RRM + HS hypertension. The microcirculation of hind limb (medial and lateral gastrocnemius, plantaris, soleus) muscles was visualized using rhodamine-labeled Griffonia simplicifolia I lectin. Tissue sections were examined by videomicroscopy and microvessel density was determined by quantitative stereology. As shown previously, mean arterial pressure increased to 160 +/- 8 mm Hg and microvessel density decreased (>30% decrease in all beds) in male RRM + HS. In contrast, mean arterial pressure of female RRM + HS rats was modestly increased from 101 +/- 2 to 118 +/- 4 mm Hg. Despite previous results showing a reduction in microvessel density of both normotensive and hypertensive male rats on a high salt diet, microvessel density of female RRM + HS rats was not reduced at either time. These results suggest that gender protection in the RRM rat extends beyond an attenuation of the increase in pressure to an immunity from microvascular rarefaction.

Animals↗