Search results for "DNA-BINDING"

Mismatch G-T binding activity and MSH2 expression is quantitatively related to sensitivity of cells to methylating agents

1998

To elucidate mechanisms involved in alkylating drug resistance, Chinese hamster cells resistant to methylating agents have been generated upon transfection with human DNA. Here it is shown that these Chinese hamster ovary (CHO) variants exhibit the tolerance phenotype: they are alkyltransferase deficient (Mex-), cross-resistant to 6-thioguanine, exhibit reduced G-T binding (MutS alpha) activity and express the mismatch repair protein MSH2 at a significantly lower level than the corresponding control. By comparing wild-type cells with different tolerant strains that show gradual differences in resistance to methylating agents, it was shown that both the G-T binding activity and the amount of…

Cellular stress induces cap-independent alpha-enolase/MBP-1 translation.

2015

AbstractMyc promoter-binding protein-1 (MBP-1) is a shorter protein variant of the glycolytic enzyme alpha-enolase. Although several lines of evidence indicate that MBP-1 acts as a tumor suppressor, the cellular mechanisms and signaling pathways underlying MBP-1 expression still remain largely elusive. To dissect these pathways, we used the SkBr3 breast cancer cell line and non-tumorigenic HEK293T cells ectopically overexpressing alpha-enolase/MBP-1. Here, we demonstrate that induced cell stresses promote MBP-1 expression through the AKT/PERK/eIF2α signaling axis. Our results contribute to shedding light on the molecular mechanisms underlying MBP-1 expression in non-tumorigenic and cancer c…

Stabilization of hsp70 mRNA on prolonged cell exposure to hypertonicity

2002

AbstractProlonged exposure of 3T3 cells to 0.5 osM hypertonic medium induced the accumulation of hsp70 mRNAs. This increase in mRNA levels required active protein synthesis. A weak and transient activation of heat shock factor 1 (HSF1) was noted, but it was temporally uncoupled to the accumulation of the hsp70 mRNAs. Nuclear run-on assay and transfection experiments showed that hsp70 gene transcription was not affected by hypertonicity. ActD chase experiments showed that during hypertonic treatment, degradation of hsp70 mRNAs was markedly reduced. This effect did not appear to be a general phenomenon since the increase in mRNA level of another gene induced by hypertonicity (ATA2 transporter…

Assessment of oxidative damage to proteins and DNA in urine of newborn infants by a validated UPLC-MS/MS approach

2014

The assessment of oxidative stress is highly relevant in clinical Perinatology as it is associated to adverse outcomes in newborn infants. This study summarizes results from the validation of an Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of the urinary concentrations of a set of endogenous biomarkers, capable to provide a valid snapshot of the oxidative stress status applicable in human clinical trials, especially in the field of Perinatology. The set of analytes included are phenylalanine (Phe), para-tyrosine (p-Tyr), ortho-tyrosine (o-Tyr), meta-tyrosine (m-Tyr), 3-NO2-tyrosine (3NO(2)-Tyr), 3-Cl-tyrosine (3Cl-T…

IL-21 Regulates the Differentiation of a Human γδ T Cell Subset Equipped with B Cell Helper Activity

2012

Vγ9Vδ2 T lymphocytes recognize nonpeptidic antigens without presentation by MHC molecules and display pleiotropic features. Here we report that coculture of Vγ9Vδ2 cells with phosphoantigen and IL-21 leads to selective expression of the transcription repressor Bcl-6 and polarization toward a lymphocyte subset displaying features of follicular B-helper T (T(FH)) cells. T(FH) like Vγ9Vδ2 cells have a predominant central memory (CD27(+)CD45RA(-)) phenotype and express ICOS, CD40L and CXCR5. Upon antigen activation, they secrete IL-4, IL-10 and CXCL13, and provide B-cell help for antibody production in vitro. Our findings delineate a subset of human Vγ9Vδ2 lymphocytes, which, upon interaction w…

Inhibition of Filamentation Can Be Used To Treat Disseminated Candidiasis

2006

ABSTRACT Candida albicans remains the leading causative agent of invasive fungal infection. Although the importance of filamentation in C. albicans pathogenesis has been extensively investigated, in vivo studies to date have been unable to dissect the role of this developmental process in the establishment of infection versus the development of active disease as characterized by damage to the host leading to mortality. To address this issue, we genetically engineered a C. albicans tet-NRG1 strain in which filamentation and virulence can be modulated both in vitro and in vivo simply by the presence or absence of doxycycline (DOX): this strain enabled us, in a prior study, to demonstrate that…

Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes

2005

Selective depletion of alloreactive T cells from stem-cell allografts should abrogate graft-versus-host disease while preserving beneficial T cell specificities to facilitate engraftment and immune reconstitution. We therefore explored a refined immunomagnetic separation strategy to effectively deplete alloreactive donor lymphocytes expressing the activation antigen CD69 upon stimulation, and examined the retainment of antiviral, antileukemic, and immunoregulatory T cells. In addition to the CD69high T cell fraction, our studies retrieved two T cell subsets based on residual CD69 expression. Whereas, truly CD69(neg) cells were devoid of detectable alloresponses to original stimulators, CD69…

NF-ATp plays a prominent role in the transcriptional induction of Th2-type lymphokines

1997

Nitic oxide promotes strong cytotoxicity of phenolic compounds against escherichia coli. The influence of antioxidant defenses

2003

[EN] The induction of mutagenic and cytotoxic effects by simple phenolics, including catechol (CAT), 3,4dihydroxyphenylacetic acid (DOPAC), hydroquinone (HQ), and 2,5-dihydroxyphenylacetic (homogentisic) acid (HGA), appears to occur through an oxidative mechanism based on the ability of these compounds to undergo autoxidation, leading to quinone formation with the production of reactive oxygen species. This is supported by the detection of such adverse effects in plate assays using Escherichia coli tester strains deficient in the OxyR function, but not in OxyR(+) strains. The OxyR protein is a redox-sensitive regulator of genes encoding antioxidant enzymes including catalase and alkyl hydro…

The triterpenoid ursolic acid ameliorates stress in Caenorhabditis elegans by affecting the depression-associated genes skn-1 and prdx2.

2021

Abstract Introduction Depression is one of the leading causes of death worldwide. Lower antioxidant concentrations and increased oxidative stress levels contribute to the development of depression. Effective and tolerable medications are urgently needed. Nrf2 and PRDX2 are promising targets in the treatment of oxidative stress and, therefore, promising for the development of novel antidepressants. Ursolic acid (UA), a natural triterpenoid found in various plants is known to exert neuroprotective and antioxidant effects. Skn-1 (which corresponds to human Nrf2) and prdx2 deficient mutants of the nematode Caenorhabditis elegans are suitable models to study the effect of UA on these targets. Ad…