RESUMO
Epithelial to Mesenchymal Transition (EMT) is an important process involved in cancer, embryogenesis and organ development. Its role in nonsyndromic cleft lip with or without cleft palate (NSCL/P) has been extensively investigated and successfully linked to the disease. In this study, we focused on a gene, CDH1, encoding for E-cadherin, a key protein in EMT. We carried out an association study on an Italian sample group, genotyping four single nucleotide variations within the CDH1 gene, in order to verify the potential role of this gene in NSCL/P etiology. Neither the haplotype nor the family-based association test revealed any association between the genotyped SNPs and the pathology. Our results demonstrate that, in our Italian sample study, the analyzed single nucleotide polymorphisms are not associated to NSCL/P.
RESUMO
Epithelial mesenchymal transformation is considered a cardinal process in orofacial development. Several molecular players appear to be involved in this delicate mechanism; the activation of LEF1 transcription factor by transforming growth factor beta 3 seems to be a key step for the correct flow of events. The failure of orofacial processes during embryonic development may provoke cleft lip and/or cleft palate malformations. The scope of the present investigation was to verify whether genetic variants at LEF1 could influence the risk of orofacial clefting. The approach was a family based association study involving a total of 512 Italian patients and their parents, 401 having cleft lip with or without cleft palate (CL/P) and 111 with cleft palate only (CPO). Haplotype association analysis provided moderate evidence of an association with clefting (p 0.01). A log-linear likelihood-based method was used to verify maternal and foetal-maternal association. An association between the maternal genotype and the occurrence of CL/P was observed at two polymorphic loci, at rs10022956 (P = 0.0049) and rs10025431 (P = 0.0065) respectively, while a foetal-maternal effect modulating the risk of clefting was found at locus rs10025431 (P = 0.0071). These data further corroborate the importance of the mother's genotype with regard to susceptibility to malformations and early-onset diseases.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Fator 1 de Ligação ao Facilitador Linfoide/genética , Feminino , Genótipo , Humanos , Itália , Polimorfismo de Nucleotídeo Único , Gravidez , População Branca/genéticaRESUMO
The FHIT gene, a member of the histidine triad gene family, is a tumor suppressor gene exhibiting deletions in the majority of human cancers. Aberrant transcripts of this gene have been found in about 50% of esophageal, stomach and colon carcinomas. Little is known about the molecular mechanisms involved in malignant transformation of the lining cells of the anus. In this study FHIT gene expression was investigated in this particular kind of human cancer. FHIT expression was comparatively analyzed at the mRNA level, by RT-PCR, in squamous anal cancers, normal anal tissue and peripheral blood samples. cDNA analyses showed variability in FHIT transcripts, without apparent effects on the predicted amino acid sequence. These different FHIT mRNAs could represent transcripts from an alternative splicing event. Our data indicate that the FHIT mRNA detected in anal cancers and in normal samples is heterogeneous. Immunohistochemical data suggest that the Fhit protein is expressed only in a fraction of the tumor cells, while it is strongly expressed in the epithelial cells of glands of the normal anal mucosa. The absence or poor expression of the Fhit protein in anal cancers suggests a role for this tumor suppressor gene product, as a risk factor, in the onset of this human cancer, as reported before for other human gastrointestinal tumors.
Assuntos
Hidrolases Anidrido Ácido/biossíntese , Neoplasias do Ânus/metabolismo , Proteínas de Neoplasias/biossíntese , Neoplasias do Ânus/genética , Sequência de Bases , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIM: To investigate the single nucleotide polymorphisms (SNPs) in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS: Analyses of CD14 -260C>T, CARD15/NOD2 3020insC, Toll-like receptor (TLR)4 +896A>G, TLR9 -1237T>C, TLR9+2848G>A, and IRAKM + 22148G>A SNPs were performed in 157 ileal-pouch anal anastomosis (IPAA) patients (79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients) and 224 Italian Caucasian healthy controls. RESULTS: No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLR9-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, oddos ratio (OR) = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group (P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3). CONCLUSION: There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriership of the CD14 -260T and TLR9 -1237C alleles in the chronic relapsing pouchitis group suggests that these markers identify a subgroup of IPAA patients with a risk of developing chronic or refractory pouchitis.
Assuntos
Receptores de Lipopolissacarídeos/genética , Pouchite/genética , Pouchite/imunologia , Receptor Toll-Like 9/genética , Adulto , Alelos , Sequência de Bases , Estudos de Casos e Controles , Doença Crônica , Bolsas Cólicas/efeitos adversos , DNA/genética , Feminino , Frequência do Gene , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Pouchite/etiologia , Recidiva , Fatores de RiscoRESUMO
The pathogenesis of cleft lip with or without cleft palate (CL/P) is complex; its onset could be due to the interaction of various genetic and environmental factors. Recently MTHFR functional polymorphisms were found to increase the risk of this common malformation; however, this finding is still debated. We investigated 110 sporadic CL/P patients, their parents and 289 unrelated controls for c.665C>T (commonly known as 677C>T; p.Ala222Val) and c.1286A>C (known as 1298A>C; p.Glu429Ala) polymorphism in the MTHFR gene. Transmission disequilibrium test (TDT) showed no distortion in allele transmission. Nevertheless, association studies revealed significant differences in allele frequencies between mothers of CL/P patients and controls. This work supports the hypothesis that a lower MTHFR enzyme activity in pregnant women, mostly related to the c.665C>T variant form, is responsible for a higher risk of having CL/P affected offspring.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Variação Genética/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Filhos Adultos , Alelos , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação/genética , Masculino , Polimorfismo Genético/genética , Fatores de Risco , SíndromeRESUMO
Signal transduction elements, including protein kinase C, have been identified in mammalian spermatozoa. In order to evaluate the pattern of expression and the subcellular localization of nine different protein kinase C isoforms in the course of spermatogenesis, we utilized quantitative electron microscopy immunocytochemistry on thin sections of rat seminiferous tubules. The results indicate a progressive reduction of the protein kinase C isoforms present in the early stages of spermatogenesis, so that in late spermatids none of them is present in the nucleus, while the isoforms alpha, gamma and beta II are specifically retained in the acrosome, the isoforms beta I and zeta in the neck, and the isoform epsilon in the tail. These isoforms, except for beta II, are maintained at the same sites in spermatozoa. Western blotting analysis indicates the presence of alpha and gamma isoforms in the head subfraction, and of beta I, zeta and epsilon isoforms in the tail subfraction of spermatozoa. These findings suggest that specific protein kinase C isoforms may be functionally involved in some events of spermatozoa differentiation and, eventually, in the fertilization process.
Assuntos
Isoenzimas/metabolismo , Proteína Quinase C/metabolismo , Espermatogênese/fisiologia , Espermatozoides/enzimologia , Animais , Western Blotting , Masculino , Microscopia Imunoeletrônica , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Espermátides/metabolismo , Espermátides/ultraestrutura , Espermatozoides/ultraestruturaRESUMO
Presence and intracellular distribution of phosphoinositide-specific phospholipase C, phosphatidylinositol 4,5-bisphosphate and protein kinase C have been investigated in rat maturing germ cells and spermatozoa. The isoforms beta 1 and gamma 1 of phosphoinositide-specific phospholipase C were immunologically identified and found to be predominantly nuclear or cytoplasmic and nuclear, respectively. The two enzymes were present in the maturing cell lineage of the seminiferous tubule, except for the nucleus of late spermatids, and absent in spermatozoa, in which, however, a phosphoinositide-specific phospholipase C activity persisted, due to yet uncharacterized enzyme(s). Protein kinase C paralleled these developmental changes, and was completely down-regulated in both total cell homogenates and isolated nuclei obtained from spermatozoa. On the contrary, phosphatidylinositol 4,5-bisphosphate, present at the nuclear level in all cell types, accumulated in the nuclei of late spermatids and spermatozoa. These data support the contention that the spermatozoon nucleus stores a lipid-dependent signaling apparatus which could be reactivated either during sperm maturation or at fertilization.
Assuntos
Células Germinativas/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Proteína Quinase C/metabolismo , Espermatogênese/fisiologia , Espermatozoides/metabolismo , Animais , Células Germinativas/ultraestrutura , Imuno-Histoquímica , Masculino , Microscopia Eletrônica , Fosfatidilinositol Diacilglicerol-Liase , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Espermatozoides/ultraestruturaRESUMO
The granulocytic differentiation of HL-60 cells induced by all-trans retinoic acid was accompanied by a progressive tyrosine phosphorylation of specific proteins in either cells or isolated nuclei. Among these phosphoproteins, we identified the Vav adaptor in whole cells as well as in the inner nuclear compartment, where the increase in its tyrosine phosphorylation level was more conspicuous. We also demonstrated the differentiation-dependent association of nuclear phosphorylated Vav to phospholipase C-gamma1 and to the p85 regulatory subunit of phosphoinositide 3-kinase. The role of the Vav/phospholipase C-gamma1/phosphoinositide 3-kinase phosphoprotein complexes in the nuclei of HL-60 induced to differentiate along the granulocytic lineage is discussed.
Assuntos
Granulócitos/metabolismo , Isoenzimas/metabolismo , Proteínas Oncogênicas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfolipases Tipo C/metabolismo , Tirosina/metabolismo , Diferenciação Celular , Núcleo Celular/metabolismo , Granulócitos/citologia , Granulócitos/enzimologia , Células HL-60 , Humanos , Fosfolipase C gama , Fosforilação , Proteínas Proto-Oncogênicas c-vavRESUMO
During organ differentiation, cell-extracellular matrix (ECM) interactions are required. The components of the ECM, such as glycosaminoglycans, fibronectin, laminin, and collagens, change in relation to cytokine and enzyme activity. Moreover, glycosaminoglycans (GAGs) are components of the ECM that play an important role in both cytokine regulation and cell activities. In this work we studied the accumulation of hyaluronic acid and chondroitin sulfate and heparan sulfate proteoglycans (PGs), beta-N-acetyl-D-glucosaminidase activity, the presence of transforming growth factor beta(2) (TGF beta(2)), and interleukin-1 (IL-1), and the localization of fibronectin, laminin, and collagen I and IV during the early stages of chick embryo lung development. We also determined the levels of hyaluronic acid, chondroitin sulfate, dermatan sulfate, and heparan sulfate GAGs and the activity of beta-N-acetyl-D-glucosaminidase with biochemical methods. Our data show that beta-N-acetyl-D-glucosaminidase activity increases in each cell, especially in the epithelial growth front at the emergence of each bronchial bud, where hyaluronic acid and IL-1 are located in the surrounding mesenchymal areas. Chondroitin sulfate and heparan sulfate PGs, fibronectin, laminin, and collagen I and IV are evident in the area near the basal membrane along the sides where the forming structures are stabilized. Biochemical data show that beta-N-acetyl-D-glucosaminidase activity increases in cells during lung development and is related to GAG decrease and to modifications of the nonsulfated/sulfated GAG ratio. These modifications could change cytokine activity and play an important role in bronchial branching development.
Assuntos
Glicosaminoglicanos/biossíntese , Glicosídeo Hidrolases/metabolismo , Interleucina-1/metabolismo , Pulmão/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Brônquios/embriologia , Brônquios/metabolismo , Embrião de Galinha , Espaço Extracelular/metabolismo , Imuno-Histoquímica , Pulmão/embriologia , Fator de Crescimento Transformador beta2RESUMO
The phospholipid involvement in the regulation of the functional and structural properties of isolated nuclei has been studied by analyzing the composition and the possible function of the nuclear matrix bound phospholipids in rat liver and murine erythroleukemic cells. The digestion of the matrix phospholipids with phospholipases results in the release of essentially all the newly replicated matrix DNA. The exogenous addition of liposomal phosphatidylserine to rat liver nuclei induces chromatin structural changes consisting in a disaggregation of the heterochromatin, probably mediated by the matrix remodeling, and in a transition from the solenoid fiber to the nucleosome filament, due to the removal of the histone H1. These effects occur through a direct interaction of phospholipid molecules with the inner nuclear components, as demonstrated by carboxyfluorescein transfer and electron microscope autoradiography.
Assuntos
Cromatina/metabolismo , DNA/metabolismo , Fosfolipídeos/farmacologia , Animais , Autorradiografia , Cromatina/efeitos dos fármacos , Cromatina/ultraestrutura , Técnicas In Vitro , Leucemia Eritroblástica Aguda/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Fosfolipases/farmacologia , Ratos , Ratos Endogâmicos , Moldes Genéticos , Transcrição GênicaRESUMO
The FHIT gene is altered in several types of tumors and abnormal expression of Fhit protein have also been reported in some preneoplastic lesions. We have determined the Fhit expression on histological samples of 26 patients affected by preneoplastic lesions who developed a gastric cancer within 2 years. The expression of the Fhit protein was always present in all preneoplastic lesions, while the Fhit protein immunostaining was distributed unevenly in 10 cases and completely lost in 6. The complete loss of Fhit expression only in areas of neoplastic low differentiation suggests that FHIT gene takes part in late gastric carcinogenesis.
Assuntos
Hidrolases Anidrido Ácido , Adenocarcinoma/metabolismo , Proteínas de Neoplasias/metabolismo , Lesões Pré-Cancerosas/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Infecções por Helicobacter/patologia , Helicobacter pylori , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
Polyamines (PA) and retinoic acid affect mammalian cell growth, differentiation and apoptosis. Retinoic acid induces granulocytic differentiation of mieloid cell lines and, during this process, is responsible for the expression of CD11b, a surface antigen. In this study we investigate the effects of retinoic acid on HL-60 cells, monitoring ornithine decarboxylase (ODC) activity (enzyme rate of PA), putrescine (PUT), spermidine (SPD), spermine (SPM) levels, CD11b myeloid surface marker differentiation, cell cycle, and apoptosis. ODC activity and PUT levels are correlated with mieloid cell differentiation induced by retinoic acid treatment. Only the ODC/PUT ratio is connected with retinoic acid treated HL-60 cells. Treated cultures show a decrease of proliferation and a cell block in the G0/G1 phase, with consequent diminished S phase. The G0/G1 and S phases are significantly related to ODC activity and to PUT and SPD behavior, whereas in differentiating condition only the decrease of PUT is related to the S phase. CD11b expression, stimulated by retinoic acid treatment, is associated with the SPM trend. Total PA behavior agrees with apoptotic cell increase after 96 h of stimulation. Our data show that retinoic acid treatment modifies ODC activity and the turnover of PA. PUT, SPD and SPM, therefore, have a different role, and may be involved in the differentiative/apoptotic program of retinoic acid treated HL-60 cells.
Assuntos
Antígeno CD11b/biossíntese , Ornitina Descarboxilase/biossíntese , Poliaminas/agonistas , Tretinoína/farmacologia , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células HL-60 , Humanos , Poliaminas/metabolismoRESUMO
Phospholipidic liposomes can influence DNA template availability for RNA synthesis when interacting with isolated nuclei by enhancing (when the phospholipids are negatively charged) or by inhibiting (when they are neutral) trascriptional activity. The analysis of the 1H-NMR relaxation behaviour of isolated nuclei, of Small Unilamellar Vesicles (SUV) and of the SUV-Nuclei system has been undertaken to elucidate the mechanism of the interaction between the nuclear core and the phospholipids.
Assuntos
Núcleo Celular/metabolismo , Lipossomos , Fosfatidilcolinas/metabolismo , Animais , Núcleo Celular/ultraestrutura , Técnica de Fratura por Congelamento , Hidrogênio , Fígado/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Masculino , Ratos , Ratos EndogâmicosRESUMO
Nonsyndromic cleft lip with or without cleft palate (CL/P) is the most common orofacial malformation, having a non-Mendelian and multifactorial aetiology. It has been shown that polymorphic variants of genes encoding key proteins of folate and methionine metabolism might be important maternal risk factors for having a child with these craniofacial anomalies. The aim of this study was to evaluate the role of two polymorphisms of the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene, the A1958G and the G401A variants, on the risk of CL/P in the Italian population. A1958G and G401A polymorphism genotyping of MTHFD1 was performed on 216 CL/P triads, (patient and parents), for this study by restriction endonuclease digestion of PCR products. Linkage disequilibrium between markers and disease was tested using both pairwise and haplotype analyses. In our case-parents triad design no significant association between MTHFD1 and the disease is evident. Our data do not support MTHFD1 involvement in CL/P onset among the Italian population.
Assuntos
Fenda Labial/enzimologia , Fenda Labial/genética , Fissura Palatina/enzimologia , Fissura Palatina/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , População Branca/genética , Alelos , Frequência do Gene , Haplótipos , Humanos , Itália , Desequilíbrio de Ligação/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Flow cytometric analysis of the transfer of liposome-encapsulated carboxyfluorescein to isolated rat liver nuclei indicated that the fluorophore is actively taken up in this form, while negligible amounts are transferred when the dye is free in the reaction medium. The kinetic analysis of the uptake indicated a time- and dose-dependent reduction of the slope in the absence of transport saturable sites on the nuclear surface and of quenching phenomena. The comparison between entire and membrane-deprived nuclei demonstrated that the initial rate of uptake was higher in the absence of the complete nuclear envelope. The intranuclear binding sites were considered on the basis of the fluorescence distribution and of quantitative estimates of the amount of linked dye. The possibility of employing flow cytometry to monitor the interactions between liposomes and isolated nuclei by means of a fluorescent probe is discussed.
Assuntos
Núcleo Celular/metabolismo , Citometria de Fluxo , Fluoresceínas/metabolismo , Lipossomos , Animais , Transporte Biológico Ativo , Fígado/metabolismo , Masculino , Ratos , Ratos EndogâmicosRESUMO
The possible involvement of anionic phospholipids in the transcriptional process was studied in isolated rat liver nuclei synthesizing RNA in the presence of phosphatidylserine, which was employed in the form of multillamellar liposomes as a means of delivering the lipid to the nuclei in aqueous medium. The divalent ion requirement for RNA synthesis and the properties of the incubation mixture were not significantly modified by the phospholipid, which increased the rate and the extent of the incorporation of 3H-UMP without changing the endogeneous degradation pattern of the product or affecting the activity of a particular RNA polymerase, as indicated by the sensitivity to amanitin. The thin layer chromatography analysis of the alkaline hydrolysates of the RNA showed that the stimulation involved an increase of the total polyribonucleotide elongation rate. The size of the product was essentially unchanged in the presence of phosphatidylserine, as demonstrated by the qualitative overlapping of the sedimentation profiles of control and lipid treated samples in formamide-sucrose gradients. The release of the H1 fraction from intact nuclei occurring with phosphatidylserine indicated that the DNA template availability was increased by a partial removal of the restrictions imposed by histones, as suggested also by the comparison with heparin and Sarkosyl. These evidences, together with the data accumulated on the occurrence of lipids in chromatin and nuclear matrix, and on their changes related to cell growth, differentiation and malignant transformation, allow a better definition of the role that phospholipids might play in regulating the DNA template availability in the cell.
Assuntos
Núcleo Celular/metabolismo , Fígado/metabolismo , Fosfatidilserinas/farmacologia , RNA/biossíntese , Amanitinas/farmacologia , Animais , Cátions Bivalentes , RNA Polimerases Dirigidas por DNA/metabolismo , Heparina/farmacologia , Cinética , Fígado/efeitos dos fármacos , Magnésio/farmacologia , Masculino , Manganês/farmacologia , Ratos , Ratos Endogâmicos , Rifamicinas/farmacologia , Uridina Monofosfato/metabolismoRESUMO
There is increasing evidence that in human obesity, particularly the abdominal phenotype, the activity of the hypothalamic-pituitary-adrenal (HPA) axis is disregulated. At least two distinct alterations have been reported: one is characterized by several neuroendocrine abnormalities and hyperresponsiveness of the HPA axis to different neuropeptides, the other is characterized by elevated cortisol traffic and probably by supranormal cortisol production. The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes interconvert cortisol and cortisone in human. Two different isoforms have been identified. A possible modification of the activity of the enzyme 11beta-HSD1 in subjects with abdominal obesity has been described in the literature. We decided to test the hypothesis that mutated isoforms of type 11beta-HSD1 protein could be responsible for alterations of cortisol metabolism in patients with abdominal obesity. A mutational screening of the whole coding sequence and exon-flanking regions of the 11B-HSD1 gene has been performed in 8 patients. The main results of our study are the exclusion of a common association of 11beta-HSD1 mutations to obesity and the identification of two novel allelic variants for the gene 11beta-HSD1 in the Italian population, not previously described in any database.
Assuntos
Abdome , Hidroxiesteroide Desidrogenases/genética , Mutação , Obesidade/enzimologia , 11-beta-Hidroxiesteroide Desidrogenases , Hormônio Adrenocorticotrópico/sangue , Adulto , Sequência de Aminoácidos , Glicemia/análise , Índice de Massa Corporal , Análise Mutacional de DNA , Éxons , Feminino , Humanos , Hidrocortisona/sangue , Hidroxiesteroide Desidrogenases/química , Insulina/sangue , Pessoa de Meia-Idade , Dados de Sequência Molecular , Obesidade/genética , Fenótipo , Reação em Cadeia da Polimerase , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Útero/enzimologiaRESUMO
H2SO4 soluble proteins extracted from nuclei incubated with phosphatidylserine multilamellar vesicles (PS MLV) have been analysed by means of two-dimensional gel electrophoresis with particular attention to the uH2A fraction. A reduction of H1, H1 degrees and proteins A5, B7, B15 and B23 has been observed in lipid treated nuclei, while the core histones, as well as uH2A are unaffected by liposome treatment. Since these proteins show in vitro the same binding affinity for PS, their behaviour appears to be related to difference in localization in the nucleosome, responsible for their variable accessibility in the chromatin. These results might explain how this phospholipid induces a decondensation of chromatin and a stimulation of RNA synthesis.
Assuntos
Núcleo Celular/efeitos dos fármacos , Proteínas Cromossômicas não Histona/metabolismo , Histonas/metabolismo , Fosfatidilserinas/farmacologia , Animais , Lipossomos , Masculino , Coelhos , Ratos , Ratos Endogâmicos , Solubilidade , Ubiquitinas/metabolismoRESUMO
The interaction between phosphatidylcholine vesicles and isolated rat liver nuclei has been examined by studying the uptake of the fluorophore carboxyfluorescein. The kinetics of transfer of the dye, analyzed by flow cytofluorimetry with a Fluorescence Activated Cell Sorter (FACS IV), indicate an efficient delivery to the nucleoplasm. The results reflect a liposome-nuclear membrane interaction which may contribute to the processes which underlie our previously described morphological and functional changes in isolated nuclei treated with phospholipids.
Assuntos
Núcleo Celular/metabolismo , Fluoresceínas/metabolismo , Lipossomos/metabolismo , Animais , Separação Celular , Citometria de Fluxo , Membrana Nuclear/metabolismo , Fosfatidilcolinas/metabolismo , RatosRESUMO
One case of Chronic Granulocytic Leukemia is reported, in which the patient showed, during a blastic crisis, an aneupolid cariotype 45, XX, t (9; 22) (q34; q11), -16. This paper emphasizes the rare involvement of the chromosome 16 in Leukemias, and stresses the high frequency of the alterations of the chromosome group E in the course of blastic crisis.