Search results for "Transporter"

Social Interactions of Dat-Het Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy

2021

Social interaction is essential for life but is impaired in many psychiatric disorders. We presently focus on rats with a truncated allele for dopamine transporter (DAT). Since heterozygous individuals possess only one non-mutant allele, epigenetic interactions may unmask latent genetic predispositions. Homogeneous “maternal” heterozygous offspring (termed MAT-HET) were born from dopamine-transporter knocked-out (DAT-KO) male rats and wild-type (WT) mothers

Synthesis and biological evaluation of new imidazo[2,1-b][1,3,4]thiadiazole derivatives: as anticancer and antibiofilm agents, and preclinical invest…

2020

Down-regulation of the MHC class I antigen-processing machinery after oncogenic transformation of murine fibroblasts

1998

Malignant transformation is often associated with genetic alterations providing tumor cells with mechanisms for escape from immune surveillance. Human and murine tumors of various origin as well as in vitro models of viral and oncogenic transformation express reduced levels of major histocompatibility complex (MHC) class I antigens resulting in decreased sensitivity to MHC class I-restricted cytotoxic T lymphocyte (CTL)-mediated lysis. We here investigate whether the suppressed MHC class I surface expression of ras-transformed fibroblasts is due to dysregulation of the genes of the antigen-processing machinery, the peptide transporters TAP-1 and TAP-2 and the proteasome subunits LMP-2 and L…

Activity of Drug Efflux Transporters in Tumor Cells Under Hypoxic Conditions

2008

Tumor cells exhibit mechanisms by which chemotherapeutic drugs can be actively pumped out of the cell (e.g., p-glycoprotein pGP, MRP1), resulting in a multidrug resistant phenotype. Many human tumors show pronounced hypoxia which can result in a local ATP depletion which in turn may compromise the efficacy of these transporters. The aim of this study was therefore to assess the transport activity and expression of drug transporters under hypoxic conditions. Prostate carcinoma cells (R3327-AT1) were exposed to hypoxia (pO2≶0.5 mmHg) for up to 24h and pump activity was determined by an efflux assay. The results showed that exposing cells to hypoxia for 3–6 h led to a moderate increase in pGP …

Screening for Solute Transporters in Plant Photosynthetic Membranes

2008

As compared to chloroplast envelope transporters, the field of thylakoid transporters is largely unexplored. There is evidence for several transport activities in the plant thylakoid membrane, but only a copper P-type ATPase and an ATP/ADP carrier have been so far identified at the gene level in Arabidopsis thaliana. Using in silico analyses, we have predicted the existence of approximately 15 thylakoid transporters, including phosphate transporters and cation channels. For experimental validation, we have used peptide- specific antibodies and functional analyses in heterologous system. These novel data are highly relevant to understand the transport network of the thylakoid membrane and it…

Dysfunction of Torr causes a Harlequin-type ichthyosis-like phenotype in Drosophila melanogaster

2019

AbstractPrevention of desiccation is a constant challenge for terrestrial organisms. Land insects have an extracellular coat, the cuticle, that plays a major role in protection against exaggerated water loss. Here, we report that the ABC transporter Torr - a human ABCA12 paralog - contributes to the waterproof barrier function of the cuticle in the fruit fly Drosophila melanogaster. We show that the reduction or elimination of Torr function provokes rapid desiccation. Torr is also involved in defining the inward barrier against xenobiotics penetration. Consistently, the amounts of cuticular hydrocarbons that are involved in cuticle impermeability decrease markedly when Torr activity is redu…

Coordinate downregulation of multiple MHC class I antigen processing genes in chemical-induced murine tumor cell lines of distinct origin

2000

In murine tumor cell lines, downregulation of MHC class I surface expression has been frequently detected, but the underlying molecular mechanisms of such deficiencies have not been defined. In this study, murine tumor cell lines of different histology derived from spontaneous or from chemical-induced tumors were analyzed for the expression of multiple components of the major histocompatibility complex (MHC) class I antigen-processing machinery (APM), including the peptide transporter TAP, the interferon (IFN)-gamma inducible proteasome subunits and several chaperones. The tumor cell lines analyzed demonstrated a heterogeneous expression pattern of various APM components. In comparison to c…

Intertissue Flow of Glutathione (GSH) as a Tumor Growth-promoting Mechanism

2011

B16 melanoma F10 (B16-F10) cells with high glutathione (GSH) content show high metastatic activity in vivo. An intertissue flow of GSH, where the liver is the main reservoir, can increase GSH content in metastatic cells and promote their growth. We have studied here possible tumor-derived molecular signals that could activate GSH release from hepatocytes. GSH efflux increases in hepatocytes isolated from mice bearing liver or lung metastases, thus suggesting a systemic mechanism. Fractionation of serum-free conditioned medium from cultured B16-F10 cells and monoclonal antibody-induced neutralization techniques facilitated identification of interleukin (IL)-6 as a tumor-derived molecule prom…

Behavioral genetics of suicidality in Bipolar Disorder: the interaction between SERT and CLOCK polymorphisms and early-life stress

Il suicidio è un problema di salute pubblica sottostimato, così come è un lutto almeno parzialmente prevenibile: ogni contributo alla conoscenza dei fattori di rischio ad esso associati possono aiutare lo sviluppo di interventi terapeutici efficaci rivolti a fasce vulnerabili della popolazione. Più del 90% delle persone che si suicidano, o provano a farlo, hanno una malattia psichiatrica diagnosticabile e circa il 60% di tutte le morti per suicidio si verificano nel contesto di un disturbo dell’umore, soprattutto di tipo bipolare. Il suicidio ha oltretutto alta familiarità: la suicidalità è ereditabile, indipendentemente dalla diagnosi associata. Lo stress è un fattore di rischio sia prossi…

Empagliflozin Induces White Adipocyte Browning and Modulates Mitochondrial Dynamics in KK Cg-Ay/J Mice and Mouse Adipocytes

2021

Background: White adipose tissue (WAT) browning is a promising target for obesity prevention and treatment. Empagliflozin has emerged as an agent with weight-loss potential in clinical and in vivo studies, but the mechanisms underlying its effect are not fully understood. Here, we investigated whether empagliflozin could induce WAT browning and mitochondrial alterations in KK Cg-Ay/J (KKAy) mice, and explored the mechanisms of its effects.Methods: Eight-week-old male KKAy mice were administered empagliflozin or saline for 8 weeks and compared with control C57BL/6J mice. Mature 3T3-L1 adipocytes were treated in the presence or absence of empagliflozin. Mitochondrial biosynthesis, dynamics, a…