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At least 289 records · Page 16Linked to original sources
PubMed1996

Differential cellular response after glutamate analog hippocampal damage.

The tissue response after brain damage implicates the cellular "activation" of astrocytes and microglia. This glial response is referred as reactive gliosis. Using immunohistochemical markers, we have analyzed the neuronal and glial response to some neurotoxic-induced lesions. We have compared the effects of two glutamate analogs, AMPA and kainic acid, with those of traumatic injury. Our data showed that the time-course of appearance, the relative contribution of and the behavior of reactive astrocytes and microglial cells were clearly different after AMPA or kainic acid administration. The immunoreactivity associated with microglia response, with respect to the immunoreactivity associated with reactive astrocytes, was higher after AMPA damage than after kainic acid treatment. In both cases, however, glial cells were more abundant than after traumatic lesions. Interestingly, the CA1 pyramidal neurons affected by AMPA and some cortical neurons affected by traumatic injury responded with an overexpression of amyloid precursor protein, whereas no neuronal response was detected after the kainic acid treatment. Our data suggest that the gliotic response is highly specific to the type of insult and heterogeneous depending on the brain area affected.

Animals↗
PubMed1998

Thrombin receptor expression and responsiveness of human monocytic cells to thrombin is linked to interferon-induced cellular differentiation.

Human thrombin has been shown to stimulate monocyte chemotaxis, phagocytosis, and interleukin (IL8) production, but the mechanisms responsible for stimulation are not well defined. In some cells, thrombin stimulation of proliferation appears to require both cleavage of the proteolytically activated receptor for thrombin (PAR1) and activation of a nonproteolytically activated thrombin receptor (N-PAR), while in others activation of either receptor alone may be sufficient for stimulation. We, therefore, have initiated studies to address thrombin receptor expression and cell responsiveness to thrombin in interferon gamma (IFNgamma)-differentiated and nondifferentiated U937 monocytic cells. Northern blot analysis shows that PAR1 expression is upregulated upon differentiation. Experiments with biotinylated and 125I-thrombin show that specific thrombin binding is dramatically increased by differentiation although it is not clear if this binding is to PAR1 or to a separate binding component such as N-PAR which is present on fibroblasts and other cells. Addition of thrombin at concentrations of 1-10 microg/ml (30-300 nM, concentrations where specific thrombin binding is observed) stimulates proliferation of IFNgamma-differentiated U937 cells but not of undifferentiated U937 cells. Thrombin also stimulates interleukin-6 (IL6) production in IFNgamma-differentiated U937 cells. Moreover, thrombin induces high levels of IL6, interleukin-1beta (IL1beta), and tumor necrosis factor-alpha (TNF alpha) production by peripheral blood mononuclear cells (PBMC) and monocytes. These results show that differentiated U937 cells and mature PBMC are responsive to thrombin whereas nondifferentiated U937 are not. Further, this responsiveness appears to correlate with expression of PAR1 and to a dramatic increase in specific thrombin binding. That thrombin stimulates cytokine production and proliferation in populations of differentiated monocytes suggests that thrombin may be an important regulator of inflammation and wound healing.

Cell Differentiation↗
PubMed2001

Expression of the urokinase plasminogen activator receptor is transiently required during "priming" of PC12 cells in nerve growth factor-directed cellular differentiation.

We previously identified the urokinase plasminogen activator receptor (UPAR) as a gene induced by nerve growth factor (NGF), but not by epidermal growth factor (EGF), in PC12 cells (Farias-Eisner et al. [2000] J. Neurosci. 20:230-239). Antisense oligonucleotides for the UPAR mRNA or an antibody directed against UPAR protein, added simultaneously with NGF, block NGF-induced morphological and biochemical differentiation of PC12 cells. In this report, we show that anti-UPAR antibody blocks morphological differentiation and the expression of two NGF-specific secondary response genes, collagenase-1 and transin, in PC12 cells only during the first 2 hr following NGF exposure. These data suggest that induced UPAR expression is required only over a short period of time following exposure to NGF for the differentiation program in PC12 cells to proceed. For two models of "primed" PC12 cells, we found that UPAR expression and function are not required for NGF-induced differentiation. UPAR and the secondary response genes collagenase-1 and transin are not induced in "primed" PC12 cells in response to NGF, and anti-UPAR antibody does not block morphological differentiation in these cells. Our data suggests that UPAR is required only transiently during the "priming" of PC12 cells in NGF-induced PC12 cell differentiation.

Animals↗
PubMed1986

Laryngeal papillomatosis is associated with a defect in cellular differentiation.

The effects of human papillomavirus infection, which can cause laryngeal papillomas, were studied in vitro in laryngeal stratified squamous epithelial cells. Interferon exposure had only minor effects on the outgrowth of primary cells from tissue fragments and the incorporation of tritiated amino acids by first-passage cells. There was a marked decrease in tritiated thymidine incorporation by papilloma cells when cultured in the presence of interferon, but no effect on thymidine incorporation by normal cells. Differentiation of laryngeal papillomas appears to be abnormal. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of keratins showed that the keratins of high relative molecular mass (Mr 51,000 and 59,000) associated with normal laryngeal differentiation were absent from papilloma tissue. Rather, both papilloma tissue and cultured papilloma cells contained a keratin of Mr 53,000 not normally present. Binding of the fluoresceinated lectin peanut agglutinin to cell surfaces suggested that there were alterations in the normal distribution of glycoproteins or glycolipids on papilloma tissues. Filaggrin, a protein synthesized by differentiating cells, was not detectable in most superficial papilloma cells after immunohistochemical staining. These studies strongly suggest that papilloma cells do not differentiate normally. We propose that this defect may be responsible for the hypertrophy of the tissue.

Adolescent↗
PubMedDate not supplied

Cell surface components of intestinal epithelial cells and their relationship to cellular differentiation.

The surfaces of the epithelial cells of the rat small intestine were studied by fluorescence microscopy using various fluorescein isothiocyanate-conjugated lectins. Throughout most of the adult intestine changes were detected in the luminal surfaces as the cells differentiate and move from the crypts to the villi. These changes in cell surface material depend upon the region of intestine in which the villi are located. By the end of the second week of postnatal development the cell surface components detected by the lectins used in this study have appeared at all levels of the small intestine. The maturational and regional differences begin to appear during the third week of postnatal development, and the adult pattern of distribution of surface components is established by 30 days after birth. By eight weeks after proximal jejunal-ileal resectioning or transposition of ileal segments to the jejunum, the epithelial cell surfaces of the relocated ileum had acquired the surface properties characteristic of the jejunal cells. However, jejunal segments transposed to the ileum maintained their original cell surface characteristics and influenced the properties of ileal cell surfaces distally adjacent to the transposed segment. The cell surface material detected by the Ricinus communis (RCAI) lectin was extracted from crypt cells of adult rat jejunum and isolated by affinity chromatography. The isolated material was found to contain at least two components, and its distribution in the jejunum was examined by fluorescence microscopy using antibodies prepared against the isolated material.

Animals↗
PubMed2005

Regulated nucleocytoplasmic transport in spermatogenesis: a driver of cellular differentiation?

This review explores the hypothesis that regulation of nucleocytoplasmic shuttling is a means of driving differentiation, using spermatogenesis as a model. The transition from undifferentiated spermatogonial stem cell to terminally differentiated spermatozoon is, at its most basic, a change in the repertoire of expressed genes. To effect this, the complement of nuclear proteins, such as transcription factors and chromatin remodelling components must change. Current knowledge of the nuclear proteins and nucleocytoplasmic transport machinery relevant to spermatogenesis is consolidated in this review, and their functional linkages are highlighted not only as a means of regulating nuclear protein composition, but also as a key mechanism regulating gene transcription and hence cell fate. Through this, we hypothesize that male germ cell differentiation is mediated through regulation of nuclear transport machinery components, and thereby of the access of critical factors to the nucleus. The importance of nucleocytoplasmic trafficking to male germ cell differentiation is discussed, using the sex-determining factors Sry and SOX9, cell cycle regulators, CREM and cofactors and the Smads as specific examples, together with the roles in gametogenesis for particular nuclear transport factors in Caenorhabditis elegans and Drosophila.

Active Transport, Cell Nucleus↗
PubMed2004

Epigenetic regulation of human telomerase reverse transcriptase promoter activity during cellular differentiation.

The human telomerase reverse transcriptase (TERT) gene is transcriptionally inactivated in most differentiated cells but is reactivated in the majority of cancer cells. To elucidate how TERT is inactivated during differentiation, we applied all-trans retinoic acid (ATRA) to induce the differentiation of human teratocarcinoma (HT) cells and human acute myeloid leukemia (HL60) cells. We first showed that TERT promoter activity decreased rapidly, which preceded a gradual loss of endogenous telomerase activity following ATRA induction. To elucidate the underlying mechanisms of the reduced TERT promoter activity during differentiation, we performed epigenetic studies on the TERT promoter and found a progressive histone hypoacetylation coupled with a gradual accumulation of methylated cytosines in the TERT promoter. We also observed that the TERT promoter was less methylated in pluripotent HT cells than in multipotent HL60 cells throughout a 12-day differentiation process. This origin-dependent epigenetic change was also confirmed in histone acetylation studies, indicating that the TERT promoter was more resistant to deacetylation in HT cells than in HL60 cells. Taken together, our results demonstrate synergistic involvement of DNA methylation and histone deacetylation in the down-regulation of TERT promoter activity that may be dependent on the origin of the cell types, and they add new insight into the way telomerase activity may be regulated during differentiation.

Acetylation↗
PubMed1993

Differential cellular effects in the toxicity of haloalkene and haloalkane cysteine conjugates to rabbit renal proximal tubules.

The relationship between the covalent binding, uptake, and toxicity produced by S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC) was investigated in suspensions of rabbit renal proximal tubules (RPT). The DCVC and TFEC at concentrations of 25 microM produced a time-dependent (1-6 hours) loss of RPT viability. The TFEC was biotransformed rapidly by beta-lyase to a reactive metabolite which bound covalently to tubular protein. Approximately 63% of the TFEC-equivalents inside the cell were bound to protein. Covalent binding of TFEC-equivalents was associated with a 30% decrease in tubular basal and state 3 respiration, a sevenfold increase in lipid peroxidation, and, ultimately, cell death. The DCVC was biotransformed rapidly to a reactive metabolite which bound covalently to tubular protein. Approximately 90% of the DCVC-equivalents inside the cell were bound covalently to tubular protein. Following exposure to 25 microM DCVC, the binding of DCVC-equivalents was associated with a 17-fold increase in lipid peroxidation but, in contrast to TFEC, had no effect on tubular respiration. However, exposure of RPT to 100 microM DCVC resulted in a ninefold increase in the binding of DCVC-equivalents and a 30% decrease in tubular state 3 respiration. The beta-lyase inhibitor aminooxyacetic acid (AOAA) blocked the covalent binding, mitochondrial dysfunction, lipid peroxidation, and cell death produced by TFEC. The AOAA decreased the covalent binding and the lipid peroxidation produced by DCVC by approximately 60-70% but had no effect on cell death.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminooxyacetic Acid↗
PubMed1993

Histone H1t: a tissue-specific model used to study transcriptional control and nuclear function during cellular differentiation.

One of the most prominent and best studied family of genes is the histone gene family. In recent years, histone gene regulation during the cell cycle of somatic cells has been studied extensively. This paper is intended to highlight and emphasize recent data concerning the tissue-specific expression of histone H1t using spermatogenesis as a model system. In this article we describe a unique DNA element within the proximal promoter of the histone H1t gene. This element has been shown to bind exclusively to nuclear proteins from pachytene spermatocytes and early spermatids. Thus, there is a strong temporal correlation between the appearance of the testis-specific DNA-binding protein and the onset of transcription of the testis-specific histone H1t gene.

Animals↗
PubMed1990

Differential cellular susceptibility to Epstein-Barr virus infection in a patient with X-linked lymphoproliferative disease.

Epstein-Barr virus (EBV) is often associated with lethal lymphoproliferative diseases in immunologically compromised individuals. Recently, we have studied a 20-month-old boy with X-linked lymphoproliferative disease (XLP) who had succumbed to infectious mononucleosis (IM) complicated by fulminant hepatitis and virus-associated hemophagocytic syndrome following EBV infection. EBV genomes were detected in peripheral blood lymphocytes (PBL), cervical and mesenteric lymph nodes, liver, spleen, thymus, and bone marrow. According to restriction endonuclease analyses, the EBV-DNA pattern was similar in all samples except for the EBV-DNA from the bone marrow. Additionally, circular EBV-DNA (suggesting a latent infection) predominated in spontaneously established lymphoblastoid cell lines (LCLs) derived from both the lymph node and cord lymphocytes co-cultured with PBL. In contrast, both circular and linear EBV-DNA (suggesting a lytic infection) were noted in spontaneously established LCLs derived from his PBL. Furthermore, LCLs derived from both the lymph node and cord lymphocytes co-cultured with PBL expressed fewer reactive cells for early antigen (EA) and viral capsid antigen (VCA) than spontaneous LCLs from his PBL, thus providing evidence for different B cellular susceptibility to EBV infection in this patient with XLP. Finally, defective EBV-specific cytotoxic T cell activity was observed in this patient. Latent EBV infected cells may easily escape immunosurveillance by the host. These findings may explain the fatal course of EBV infection in this patient.

Antigens, Viral↗
PubMed2003

The expression of methyl CpG binding factor MeCP2 correlates with cellular differentiation in the developing rat brain and in cultured cells.

Mutations in the MeCP2 gene cause Rett syndrome, a neurologic condition affecting primarily young girls. To gain insight into the normal function of MeCP2, we examined its temporal and spatial expression patterns, and immunoreactive prevalence, during late embryonic and perinatal brain development. MeCP2 mRNA was detected in most regions of the developing rat brain by the late embryonic stage. Regions displaying the strongest mRNA expression include the hippocampus, cortex, and cerebellum, and moderate expression was observed in most other brain regions. At the protein level, MeCP2 was strongly expressed in adult forebrain neurons, but was not detected in astrocytes. The nonubiquitous expression of MeCP2 was also observed in the embryonic cortex, as about one-third of acutely dissociated embryonic day 14 neuroepithelial cells failed to stain with MeCP2. To test whether MeCP2 expression correlates with neuronal differentiation, colocalization of MeCP2 expression with either the precursor cell marker nestin or the young neuronal marker beta-III tubulin was examined in the same acutely dissociated cortical cells. Although strong MeCP2 expression was detected in approximately 75% of beta-III tubulin-positive cells, only about 25% of nestin-positive precursor cells were MeCP2 positive. Further support for a correlation of MeCP2 expression with cell differentiation was observed in culture, where Western blot analysis during the in vitro differentiation of PC12, NG108-15, and SH-SY5Y cells revealed that MeCP2 levels increased as the cells acquired a more differentiated phenotype. This increase was associated with differentiation, as MeCP2 expression levels did not vary within different phases of the cell cycle. Taken together, these data support a role for MeCP2 in the establishment and/or maintenance of neuronal maturity.

Animals↗