SEARCH · PubMed Health

Results for “RB1”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 91 records · Page 5Linked to original sources

PubMed1996

Influences of ginsenosides Rb1 and Rg1 on reversible focal brain ischemia in rats.

AIM: To study the influences of ginsenosides Rb1 and Rg1 (active components of the total saponins of Panax ginseng) on the brains against ischemia-reperfusion injury. METHODS: Rat focal cerebral ischemia was induced by reversible middle cerebral artery occlusion (MCAO) without craniectomy. The influences of ginsenoside Rb1 and Rg1 on infarct size (IS), neurologic deficit (ND) and the contents of calcium and potassium in the infarct were observed. RESULTS: In a 2-h ischemia, Rb1 10-40 mg.kg-1 i.v. 30 min before MCAO decreased IS by 20%-49% and ND score from 5.1 to 4.1-2.3, and inhibited Ca accumulation and K loss by 22%-50% and 18-37%, respectively; Rb1 10-40 mg.kg-1 i.v. immediately after MCA was recanalized decreased IS by 12%-35% and ND score from 5.2 to 4.3-3.3, and inhibited Ca accumulation and K loss by 10%-40% and 17%-30%, respectively. In permanent ischemia, Rb1 40 mg.kg-1 i.v. reduced IS, ND, Ca accumulation and K loss. However, Rg1 40 mg.kg-1 i.v. did not show effect on both permanent and 2-h MCAO. CONCLUSIONS: Rb1 protected brain from ischemic and reperfusion injuries.

Animals↗

PubMed1996

[Mechanism of action of ginsenoside Rb1 in decreasing intracellular Ca2+].

Using fluorescent probe Fura-2/AM, ginsenoside Rb1 (10, 50 and 100 mumol.L-1) was shown to dose-dependently reduce intracellular Ca2+ concentration of freshly dissociated brain cells isolated from newborn rats. It was also found to increase the fluidity of synaptosome membrane impaired by FeSO4-Cystein. Rb1 (10 mumol.L-1) shifted the dose-response curve to the right and decreased the maximal response in isolated mouse tail artery. Rb1 (10 and 100 mumol.L-1) was also found to reduce 5-HT-induced contraction of isolated rat basilar artery. With the whole-cell patch clamp technique, Rb1 (100 mumol.L-1) was shown to have no obvious effect on calcium current and potassium current. However, Rb1 was shown to increase Na(+)-K+ ATPase and Ca(2+)-Mg2+ ATPase activities at low dose in rat cerebral cortical synaptosomes. The results indicate that decrease of [Ca2+]i by Rb1 may be attributed to increase of ATPase activity.

Animals↗

PubMed2005

Conservation of the RB1 gene in human and primates.

Mutations in the RB1 gene are associated with retinoblastoma, which has served as an important model for understanding hereditary predisposition to cancer. Despite the great scrutiny that RB1 has enjoyed as the prototypical tumor suppressor gene, it has never been the object of a comprehensive survey of sequence variation in diverse human populations and primates. Therefore, we analyzed the coding (2,787 bp) and adjacent intronic and untranslated (7,313 bp) sequences of RB1 in 137 individuals from a wide range of ethnicities, including 19 Asian Indian hereditary retinoblastoma cases, and five primate species. Aside from nine apparently disease-associated mutations, 52 variants were identified. They included six singleton, coding variants that comprised five amino acid replacements and one silent site. Nucleotide diversity of the coding region (pi=0.0763+/-1.35 x 10(-4)) was 52 times lower than that of the noncoding regions (pi=3.93+/-5.26 x 10(-4)), indicative of significant sequence conservation. The occurrence of purifying selection was corroborated by phylogeny-based maximum likelihood analysis of the RB1 sequences of human and five primates, which yielded an estimated ratio of replacement to silent substitutions (omega) of 0.095 across all lineages. RB1 displayed extensive linkage disequilibrium over 174 kb, and only four unique recombination events, two in Africa and one each in Europe and Southwest Asia, were observed. Using a parsimony approach, 15 haplotypes could be inferred. Ten were found in Africa, though only 12.4% of the 274 chromosomes screened were of African origin. In non-Africans, a single haplotype accounted for from 63 to 84% of all chromosomes, most likely the consequence of natural selection and a significant bottleneck in effective population size during the colonization of the non-African continents.

Animals↗

PubMed2005

Spectrum of gross deletions and insertions in the RB1 gene in patients with retinoblastoma and association with phenotypic expression.

Quantitative multiplex PCR and genomic real-time PCR were used to complete an RB1 mutation analysis in 57 of 433 and 72 of 262 patients with hereditary and isolated unilateral retinoblastoma, respectively. These patients were selected because in previous analyses, which focused mainly on the identification of point mutations, no RB1 mutation was found. We identified gross deletions and insertions in peripheral blood DNA from 26 of 57 patients (46%) with hereditary retinoblastoma, and in six of 72 patients (8.3%) with isolated unilateral disease. In addition, we identified 32 somatic mutations in tumor DNA from 31 of 72 patients (43%) with isolated unilateral retinoblastoma. Together with our previous results, we found that gross RB1 alterations were present in the peripheral blood DNA from 65 of 433 (15%) and 17 of 262 (6.5%) patients with bilateral or familial and isolated unilateral retinoblastoma, respectively. Including reported gross deletions, an analysis of the frequency of breakpoints per intron length shows higher densities in introns 13, 16, 23, and 24. Genotype-phenotype analyses showed that on the whole, carriers of gross deletions develop fewer retinoblastomas compared to patients who are heterozygous for other types of RB1 null mutations. Specifically, carriers of cytogenetic and submicroscopic whole gene deletions often have unilateral tumors only. By contrast, almost all patients with gross deletions with one breakpoint in RB1 have bilateral retinoblastoma.

DNA Mutational Analysis↗

PubMed2001

Ginsenoside Rb1 and Rg1 improve spatial learning and increase hippocampal synaptophysin level in mice.

We investigated the cognition enhancing effects of ginsenoside Rb1 and Rg1. Mice were trained in a Morris water maze following injection (i.p.) of Rb1 (1 mg/kg) or Rg1 (1 mg/kg) for 4 days. Both Rb1- and Rg1-injected mice showed enhanced spatial learning compared to control animals. The hippocampus, but not the frontal cortex, of treated mice contained higher density of a synaptic marker protein, synaptophysin, compared to control mice. Electrophysiological recordings in hippocampal slices revealed that Rb1 or Rg1 injection did not change the magnitude of paired-pulse facilitation or long-term potentiation. Our results suggest that Rb1 and Rg1 enhance spatial learning ability by increasing hippocampal synaptic density without changing plasticity of individual synapses.

Animals↗

PubMed1999

Purification and characterization of two amine N-sulfotransferases, AST-RB1 (ST3A1) and AST-RB2 (ST2A8), from liver cytosols of male rabbits.

Two sulfotransferases (STs), designated as AST-RB1 (ST3A1) and AST-RB2 (ST2A8), with high a amine N-sulfonating activity, were purified from male rabbit liver cytosols. AST-RB1 and AST-RB2 were purified to homogeneity by the anion-exchange, affinity, and hydroxyapatite chromatography. The N-terminus of both enzymes were blocked. The subunit molecular mass of both enzymes was estimated to be 34 kDa on SDS-PAGE. AST-RB1 efficiently catalyzed N-sulfonation of alicyclic, alkyl, and arylamines such as 4-phenyl-1,2,3, 6-tetrahydropyridine, 1-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-piperazine, desipramine, and aniline, whereas its catalytic activities toward 2-naphthol and dehydroepiandrosterone (DHEA) were very low. On the other hand, AST-RB2 efficiently catalyzed sulfonation of desipramine and DHEA, but had no activity toward 2-naphthol. Amino acid sequences of peptide fragments derived from the purified AST-RB1 showed no significant homology with previously reported STs, but those from the purified AST-RB2 shared a high similarity with those of the ST2 family. Both enzymes were expressed specifically in the liver. The present results strongly suggest that the purified AST-RB1 is a novel enzyme in terms of structure and catalytic properties showing high selectivity for amine substrates, and AST-RB2 is a quite unique from among ST2A enzymes of other species in its substrate specificity.

Amines↗

PubMed2005

Rb1cc1 is critical for myoblast differentiation through Rb1 regulation.

Rb1-inducible coiled-coil 1 (Rb1cc1) expressed at high levels is associated with the maturation of human embryonic musculoskeletal cells. To clarify the molecular role of Rb1cc1 in muscular differentiation, we investigated the expression of Rb1cc1 and other genes that regulate differentiation in murine embryonic tissues and in C2C12 myoblasts. We also evaluated the effects of RNA interference (RNAi)-mediated Rb1cc1 knockdown on C2C12 myoblast differentiation. After Rb1cc1, Rb1 and myosin heavy chain (Myhc) were expressed in mouse embryonic muscles. The synchronous expression of Rb1cc1 and Rb1 predicted Myhc expression during C2C12 myoblast differentiation. RNAi-mediated knockdown of Rb1cc1 led to Rb1 suppression, and C2C12 myoblasts failed to differentiate. These results indicated that Rb1cc1 is a potent regulator of the Rb1 pathway and a novel mediator that plays a crucial role in muscular differentiation. Rb1cc1 expression is, thus, a prerequisite for myogenic differentiation.

Animals↗

PubMed2005

Transformation of ginsenosides Rb1 and Re from Panax ginseng by food microorganisms.

Ginsenosides Rb1 and Re, respectively belonging to the major protopanaxadiol and protopanaxatriol ginsenosides, were transformed using cell-free extracts from food microorganisms. Rb1 was transformed into compound K via Rd and F2 by Bifidobacterium sp. Int57, Bif. sp. SJ32, Aspergillus niger and A. usamii. Lactobacillus delbrueckii, and Leuconostoc paramesenteroides transformed Rb1 into Rh2 via Rd and F2. Bifidobacterium sp. SH5 transformed Rb1 into F2 via Rd. Re was transformed into Rh1 via Rg2 by Bif. sp. Int57 and Bif. sp. SJ32. A. niger transformed Re into Rh1 via Rg1. A. usamii transformed Re into Rg2. Transformation of Rb1 proceeded at a higher rate and needed less amount of enzymes than that of Re. Taken together, these processes would allow a specific bioconversion process possible to obtain specific ginsenosides using an appropriate combination of ginsenoside substrates and specific microbial enzymes.

Aspergillus↗

PubMed2006

Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor.

Ginsenosides have been shown to stimulate nitric oxide (NO) production in aortic endothelial cells. However, the signaling pathways involved have not been well studied in human aortic endothelial cells. The present study was designed to examine whether purified ginsenoside Rb1, a major active component of ginseng could actually induce NO production and to clarify the signaling pathway in human aortic endothelial cells. NO production was rapidly increased by Rb1. The rapid increase in NO production was abrogated by treatment with nitric oxide synthetase inhibitor, L-NAME. Rb1 stimulated rapid phosphorylation of Akt (Ser473), ERK1/2 (Thr202/Thr204) and eNOS (Ser1177). Rapid phosphorylation of eNOS (Ser1177) was prevented by SH-5, an Akt inhibitor or wortmannin, PI3-kinase inhibitor and partially attenuated by PD98059, an upstream inhibitor for ERK1/2. Interestingly, NO production and eNOS phosphorylation at Ser1177 by Rb1 were abolished by androgen receptor antagonist, nilutamide. The results suggest that PI3kinase/Akt and MEK/ERK pathways and androgen receptor are involved in the regulation of acute eNOS activation by Rb1 in human aortic endothelial cells.

Amino Acid Sequence↗

PubMed2006

Ginsenoside Rb1 promotes neurotransmitter release by modulating phosphorylation of synapsins through a cAMP-dependent protein kinase pathway.

Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), has been extensively used in traditional oriental medicine for the prevention and treatment of aging-related disorders for over 2000 years. Accumulating evidence suggests that ginsenosides such as Rg1 and Rb1, which are the pharmacologically active ingredients of ginseng, modulate neurotransmission. Synapsins are abundant phosphoproteins essential for regulating neurotransmitter release. All synapsins contain a short amino-terminal domain A that is highly conserved and phosphorylated by cAMP-dependent protein kinase (PKA), which plays a key role in regulating neurotransmitter release. In the present study, we demonstrated that both Rg1 and Rb1 increased neurotransmitter release in undifferentiated and differentiated PC12 cells. However, in the presence of the PKA inhibitor H89, Rg1, but not Rb1, still induced neurotransmitter release. Moreover, Rb1, but not Rg1, enhanced the phosphorylation of synapsins via PKA pathway. In summary, Rb1 promotes neurotransmitter release by increasing the phosphorylation of synapsins through the PKA pathway, whereas the similar effects observed with Rg1 are independent of the phosphorylation of synapsins.

Animals↗

PubMed2002

Identification of novel mutations in the RB1 gene in Mexican patients with retinoblastoma.

Retinoblastoma (RB) is a childhood tumor of the eye with an average incidence of one case in every 15,000-20,000 live births and occurs in sporadic or hereditary form. This cancer results from loss or inactivation of the RB1 gene located at 13q14.1. This gene encodes for a 110 Kd nuclear phosphoprotein (pRB) that plays a major role in cell proliferation control. Different types of mutations in the RB1 gene have been reported, but point mutations are the most common. There are no molecular studies on RB1 gene mutation in Mexican patients. In this study, 19 patients with bilateral or unilateral RB were analyzed. Genetic and cytogenetic studies were carried out. Detection of RB1 gene mutations was done using single-strand conformational polymorphism (SSCP). Five conformational polymorphisms were identified in different exons. In all cases, SSCP sequence showed new non-described mutations that produced a frameshift on the open reading frame. The identification of mutations in the RB1 gene contributes to basic knowledge of this neoplasia and permits the possibility to offer adequate genetic counseling to relatives at risk.

Base Sequence↗

PubMed1989

Structural alterations of the RB1 gene in human soft tissue tumours.

Sixty-nine primary soft tissue tumours were examined for alterations of the RB1 gene which has previously been implicated in the genesis of retinoblastoma. In three tumours loss of both alleles of this gene (homozygous deletion) was detected. Two of these, both leiomyosarcomas, contained a chromosomal breakpoint within the RB1 gene, while in the third tumour, a radiation induced sarcoma, complete deletion was observed. Using a probe that detects a polymorphic locus within the RB1 gene we found loss of only one allele (heterozygous deletion) in 33% of soft tissue sarcomas examined, including two leiomyosarcomas, a malignant peripheral nerve sheath tumour, a rhabdomyosarcoma and a chondrosarcoma. When taken together our results suggest that alterations of the RB1 locus may play an important part in the pathogenesis of soft tissue tumours and particularly in leiomyosarcomas which accounted for four of the eight RB1 alterations observed in this study.

Alleles↗

PubMed1994

Loss of the retinoblastoma susceptibility gene (RB1) is a frequent and early event in prostatic tumorigenesis.

Loss of the RB1 gene is an important event in the initiation and progression of many tumours. Prostate tissue from 43 patients with prostate cancers and ten with benign prostatic hypertrophy (BPH) were studied for loss of heterozygosity of the RB1 gene. Four intragenic polymorphic loci were studied with two techniques. These were restriction fragment length polymorphism (RFLP). Southern blotting and hybridisation with the p123m1.8 and p68RS2.0 probes (to introns 1 and 17 respectively) and also the polymerase chain reaction (PCR) to amplify loci within introns 17 and 20. Protein product (pRB) expression was determined by immunohistochemistry using the NCL-RB antibody in nine patients with cancer and four patients with BPH. Loss of heterozygosity was found in 24 out of 40 (60%) informative patients with cancer. Loss of RB1 occurred with a similar frequency in early-stage and low-grade cancers as in more advanced cancers. Loss of RB1 was also found in one patient with BPH. Expression of pRB was completely absent from seven cancers and markedly reduced in the other two, while nuclear pRB staining was always present in areas of BPH, whether alongside cancer-containing tissue or with BPH alone. We conclude that loss of RB1 is an early event in prostatic tumorigenesis.

Base Sequence↗

PubMed2006

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia.

In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene.

Aged↗

PubMed2005

Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin.

Here, we show a role for the RB1 family proteins in directing full heterochromatin formation. Mouse embryonic fibroblasts that are triply deficient for RB1 (retinoblastoma 1), RBL1 (retinoblastoma-like 1) and RBL2 (retinoblastoma-like 2) - known as TKO cells - show a marked genomic instability, which is coincidental with decreased DNA methylation, increased acetylation of histone H3 and decreased tri-methylation of histone H4 at lysine 20 (H4K20). Chromatin immunoprecipitation showed that H4K20 tri-methylation was specifically decreased at pericentric and telomeric chromatin. These defects are independent of E2F family function. Indeed, we show a direct interaction between the RB1 proteins and the H4K20 tri-methylating enzymes Suv4-20h1 and Suv4-20h2, indicating that the RB1 family has a role in controlling H4K20 tri-methylation by these histone methyltransferases. These observations indicate that the RB1 family is involved in maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin, linking tumour suppression and the epigenetic definition of chromatin.

Animals↗

PubMed2005

Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor.

Mutations in the gene encoding the retinoblastoma tumor suppressor predispose humans and mice to tumor development. Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of one or two Nras alleles is shown to significantly reduce the severity of pituitary tumors arising in Rb1(+/-) animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1(+/-) mice progress to metastatic medullary carcinomas after loss of Nras. In Rb1(+/-)Nras(+/-) animals, distant medullary thyroid carcinoma metastases are associated with loss of the remaining wild-type Nras allele. Loss of Nras in Rb1-deficient C cells results in elevated Ras homolog family A (RhoA) activity, and this is causally linked to the invasiveness and metastatic behavior of these cells. These findings suggest that the loss of the proto-oncogene Nras in certain cellular contexts can promote malignant tumor progression.

Adenocarcinoma↗

PubMed2005

Mutations in Rb1 pathway-related genes are associated with poor prognosis in anaplastic astrocytomas.

Anaplastic astrocytoma (AA, WHO grade III) is, second to Glioblastoma, the most common and most malignant type of adult CNS tumour. Since survival for patients with AA varies markedly and there are no known useful prognostic or therapy response indicators, the primary purpose of this study was to examine whether knowledge of the known genetic abnormalities found in AA had any clinical value. The survival data on 37 carefully sampled AA was correlated with the results of a detailed analysis of the status of nine genes known to be involved in the development of astrocytic tumours. These included three genes coding for proteins in the p53 pathway (TP53, p14(ARF)and MDM2), four in the Rb1 pathway (CDKN2A, CDKN2B, RB1 and CDK4) and PTEN and EGFR. We found that loss of both wild-type copies of any of the three tumour suppressor genes CDKN2A, CDKN2B and RB1 or gene amplification of CDK4, disrupting the Rb1 pathway, were associated with shorter survival (P=0.009). This association was consistent in multivariate analysis, including adjustment for age (P=0.013). The findings suggest that analysis of the genes coding for Rb1 pathway components provides additional prognostic information in AA patients receiving conventional therapy.

Adolescent↗

PubMed1997

Induction of apoptosis in Mv1Lu cells by expression of competitive RB1 mutants.

The Retinoblastoma tumor suppressor gene (RB1) plays a role in a variety of human cancers. Experimental analyses have indicated that the protein product of the RB1 gene (pRb) plays a role in cell cycle regulation. pRb function is dependent on its ability to bind to cellular factors, which is facilitated by multiple protein binding domains within pRb. Mutations within these domains which eliminate the ability of pRb to bind its targets result in loss of function. Although loss of pRb function may lead to uncontrolled cellular proliferation, tumorigenesis is not the only response to pRb inactivation. Examination of various tissues from RB1-nullizygous mouse embryos showed problems in differentiation and induction of apoptosis, suggesting that the ultimate response to the loss of pRb is influenced by cellular context. It has previously been demonstrated in RB1-negative Saos-2 cells that co-expression of the C-terminal domain of pRb with wildtype pRb resulted in escape from G1 arrest and continued cell cycling. In this paper we demonstrate that in RB1-positive Mv1Lu cells, expression of the A/B pocket region or the N-terminus (when combined with a nuclear localization signal), but not the C-terminal domain, is able to competitively disrupt the function of the endogenous pRb, and that the result of this disruption is apoptosis.

Animals↗