Search results for "Downregulation"

p53-Mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y.

2008

The tumor suppressor protein p53 triggers many of the cellular responses to DNA damage by regulating the transcription of a series of downstream target genes. p53 acts on the promoter of the target genes by interacting with the trimeric transcription factor NF-Y. H ferritin promoter activity is tightly dependent on a multiprotein complex called Bbf; on this complex NF-Y plays a major role. The aim of this work was to study the modulation of H ferritin expression levels by p53. CAT reporter assays indicate that: (i) p53 overexpression strongly downregulates the transcriptional efficiency driven by an H ferritin promoter construct containing only the NF-Y recognition sequence and that the phe…

Gene regulatory networks elucidating Huanglongbing disease mechanisms

2013

Next-generation sequencing was exploited to gain deeper insight into the response to infection by Candidatus liberibacter asiaticus (CaLas), especially the immune disregulation and metabolic dysfunction caused by source-sink disruption. Previous fruit transcriptome data were compared with additional RNA-Seq data in three tissues: immature fruit, and young and mature leaves. Four categories of orchard trees were studied: symptomatic, asymptomatic, apparently healthy, and healthy. Principal component analysis found distinct expression patterns between immature and mature fruits and leaf samples for all four categories of trees. A predicted protein - protein interaction network identified HLB-…

Correlation study of GAPDH, Bcl-2, and Bax protein immunoexpression in patients with colorectal adenocarcinoma.

2018

Introduction Colorectal cancer (CRC) is the third and second most commonly diagnosed cancer worldwide in males and females, respectively. Despite prominent progress in diagnosis and treatment, the recurrence rates are still high. A tumour hypoxic environment leads to an increase in glycolytic metabolism. The crucial intermediate component of glycolysis, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), could play a significant role in cancer progression. An increased level of GAPDH has been described in oncogene-induced transformation and anti-apoptotic function. In other studies, GAPDH has been involved in apoptosis induction. Aim We examined colorectal adenocarcinoma samples to assess the…

Upregulated MicroRNAs 342 and 15a Mediate Host-Pathogen Interaction in Pneumococcal Community-Acquired Pneumonia

2020

Loss of Neuroglobin Expression Alters Cdkn1a/Cdk6-Expression Resulting in Increased Proliferation of Neural Stem Cells

2018

Abstract: In the quest to unravel its functional significance, neuroglobin (Ngb), a brain-specific neuroprotective protein, has recently been proposed as an actor in neurodevelopment. As neural stem cells (NSCs) are fundamental during brain development, the present study aimed at investigating the role of Ngb in the growth and proliferation of NSCs by comparing an Ngb-floxed (Ngb(fl)-)NSC line, equivalent to the wild-type cellular situation, with an in-house created Ngb knockout (Ngb(KO)-)NSC line. Ngb(KO)-NSCs were characterized by an increased growth and proliferation capacity in vitro, supported by RNA sequencing and western blot results reporting the downregulation of Cdkn1a and the upr…

Multiple modes of cell death in neuroendocrine tumors induced by artesunate.

2020

Abstract Background The paucity of effective treatment in neuroendocrine tumors (NETs) encouraged us to investigate the therapeutic value of artesunate (ART) promised by its inhibitory effect against various tumors and broad safety profile. Methods We evaluated the impact of ART on three NET cell lines, BON-1, QGP-1 and NCI-H727 on cellular and molecular levels. Results Our results showed that ART induced endoplasmic reticulum (ER) stress through phosphorylation of eIF2α, which further gave rise to autophagy in all three NET cell lines. Specifically, apoptosis and ferroptosis were also observed in BON-1 cells, which made BON-1 cell line more vulnerable upon ART treatment. The different sens…

ER stress in human hepatic cells treated with Efavirenz: Mitochondria again

2013

Background & Aims ER stress is associated with a growing number of liver diseases, including drug-induced hepatotoxicity. The non-nucleoside analogue reverse transcriptase inhibitor Efavirenz, a cornerstone of the multidrug strategy employed to treat HIV1 infection, has been related to the development of various adverse events, including metabolic disturbances and hepatic toxicity, the mechanisms of which remain elusive. Recent evidence has pinpointed a specific mitochondrial effect of Efavirenz in human hepatic cells. This study assesses the induction of ER stress by Efavirenz in the same model and the implication of mitochondria in this process. Methods Primary human hepatocytes and Hep3B…

γδ T cells as a potential tool in colon cancer immunotherapy

2014

γδ T cells are capable of recognizing tumor cells and exert potent cellular cytotoxicity against a large range of tumors, including colon cancer. However, tumors utilize numerous strategies to escape recognition or killing by patrolling γδ T cells, such a downregulation of NKG2D ligands, MICA/B and ULBPs. Therefore, the combined upregulation of T-cell receptorand NKG2D ligands on tumor cells and induction of NKG2D expression on γδ T cells may greatly enhance tumor killing and unlock the functions of γδ T cells. Here, we briefly review current data on the mechanisms of γδ T-cell recognition and killing of colon cancer cells and propose that γδ T cells may represent a promising target for the…

Modulation of Base Excision Repair Alters Cellular Sensitivity to UVA1 but not to UVB¶

2007

Abstract Oxidative DNA damage has been implicated in some of the biological properties of UVA but so far not in the acute photosensitivity or cellular sensitivity. In contrast to pyrimidine dimers, oxidative DNA damage is predominantly processed by base excision repair (BER). In order to further clarify the role of oxidative DNA damage and its repair in the acute cellular response to UV light, we studied UVA1 and UVB sensitivities in three different cell model systems with modified BER. 8-Oxoguanine-DNA-glycosylase 1–/– (OGG1–/–) mouse embryonal fibroblasts and human fibroblasts in which BER was inhibited by incubation with methoxyamine were hypersensitive to UVA1, in particular to low dose…

Brain erythropoietin fine-tunes a counterbalance between neurodifferentiation and microglia in the adult hippocampus

2021

In adult cornu ammonis hippocampi, erythropoietin (EPO) expression drives the differentiation of new neurons,independent of DNA synthesis, and increases dendritic spine density. This substantial brain hardwareupgrade is part of a regulatory circle: during motor-cognitive challenge, neurons experience ‘‘functional’’hypoxia, triggering neuronal EPO production, which in turn promotes improved performance. Here, weshow an unexpected involvement of resident microglia. During EPO upregulation and stimulated neurodifferentiation,either by functional or inspiratory hypoxia, microglia numbers decrease. Treating mice with recombinanthuman (rh)EPO or exposure to hypoxia recapitulates these changes and…