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Epigenetic marks reduce erythrocyte uptake of antimalarials

ABSTRACT: Acquired antimalarial drug resistance produces treatment failures and has led to periods of global disease resurgence. In P. falciparum, resistance is known to arise through genome-level changes such as mutations and gene duplications. We now report an epigenetic resistance mechanism involving genes responsible for the plasmodial surface anion channel, a nutrient channel that also transports ions and antimalarial compounds at the host erythrocyte membrane. Two blasticidin S-resistant lines exhibited markedly reduced expression of clag

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE47579 | GEO | 2013/06/03

SECONDARY ACCESSION(S): PRJNA206190

REPOSITORIES: GEO

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Epigenetic marks reduce erythrocyte uptake of antimalarials

Project description:Acquired antimalarial drug resistance produces treatment failures and has led to periods of global disease resurgence. In P. falciparum, resistance is known to arise through genome-level changes such as mutations and gene duplications. We now report an epigenetic resistance mechanism involving genes responsible for the plasmodial surface anion channel, a nutrient channel that also transports ions and antimalarial compounds at the host erythrocyte membrane. Two blasticidin S-resistant lines exhibited markedly reduced expression of clag Mutant FCB-br1 and wild-type FCB samples were hybridized to seven arrays (biological repeats) using forward (n=2) and reverse (n=5) fluoro.

2013-06-03 | E-GEOD-47579 | biostudies-arrayexpress

Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation

Project description:Members of the leucine-rich repeat-containing 8 (LRRC8) protein family, composed of the five LRRC8A-E isoforms, are pore-forming components of the volume-regulated anion channel (VRAC), which is activated by cell swelling and transports halide anions and small organic compounds. Despite the recent availability of the cryo-EM structures of homo-hexameric LRRC8A, the structural basis of how LRRC8 isoforms other than LRRC8A contribute to the functional diversity of VRAC has remained elusive. In this study, we confirmed the absence of LRRC8 isoforms in the purified HsLRRC8D using mass spectrometry, and the structure of the HsLRRC8D homomer was analyzed using the cryo-EM. This work provides structural insights into the functional diversity of the LRRC8 protein family.

2020-05-27 | PXD018780 | Pride

RNA Seq of wild-type and VPS35-D620N-expressing SH-SY5Y cells

Project description:SH-SY5Y were created to stably express wild-type or VPS35-D620N (CMV-promoter driven) using a lentiviral vector (Vira power). Non-transduced cells were eliminated with blasticidin resistance gene included in viral cassette

2018-07-11 | GSE116900 | GEO

Analysis of Drug Resistant Cell Lines

Project description:Analysis of Drug transports as a mechanism of resistance to aurora kinase inhibition Parental and Taxol-resistant cell lines are compared for gene expression profile differences.

2013-06-22 | GSE47435 | GEO

Analysis of Drug Resistant Cell Lines

2013-06-22 | E-GEOD-47435 | biostudies-arrayexpress

TMC4 is a novel chloride channel involved in high-concentration salt taste sensation

Project description:Taste substances are received by taste receptors expressed in taste cells. “Salty taste” sensation is evoked when sodium and chloride ions are present together in the oral cavity. The presence of an epithelial cation channel that receives Na+ has previously been reported. However, no molecular entity involving Cl- receptors has been elucidated. We report the strong expression of transmembrane channel-like 4 (TMC4) in the circumvallate and foliate papillae projected to the glossopharyngeal nerve, mediating a high-concentration of NaCl. Electrophysiological analysis using HEK293T cells revealed that TMC4 was a voltage-dependent Cl- channel and the consequent currents were completely inhibited by NPPB, an anion channel blocker. This channel could be activated without an increase in intracellular calcium ion. TMC4 allowed permeation of organic anions including gluconate, but their current amplitudes at positive potentials were less than that of Cl-. Tmc4-deficient mice showed significantly weaker glossopharyngeal nerve response to high-concentration of NaCl than the wild-type littermates. These results indicated that TMC4 is a novel chloride channel that responds to high-concentration of NaCl.

2021-09-14 | GSE175806 | GEO

Molecular Insights into the Inhibition of Proton-Activated Chloride Channel by Transfer RNA

Project description:The proton-activated chloride (PAC) channel (also known as acid-sensitive outwardly rectifying anion channel, ASOR) plays a critical role in acid-induced cell death and endocytosis. However, little is known about the regulatory factors and binding partners of PAC. In this study, we discovered that transfer RNA (tRNA) interacts directly with PAC as an unexpected binding partner. Using cryo-electron microscopy, we determined that two PAC trimers and one co-purified tRNA molecule form a stable complex via a highly conserved KR motif, representing the closed conformation. tRNA is located on the intracellular side of PAC, blocking the channel pores. Furthermore, electrophysiological data showed that tRNA modulates chloride currents and channel open probability of PAC, thus protecting against acid-induced cell death. Our study provides insight into the regulation of PAC activity by cytosolic tRNA and extends the role of tRNAs in pathological and physiological events.

2024-06-28 | GSE216637 | GEO

Loss of voltage dependent anion channel 1 affects mitochondrial bioenergetics in rat dopamine cells

Project description:Loss of voltage dependent anion channel 1 affects mitochondrial bioenergetics in rat dopamine cells

| PRJNA486658 | ENA

Loss of GPHR in the brain

Project description:The Golgi apparatus plays a central role in the protein glycosylation where it is required for secretory trafficking. Abnormal morphology of the Golgi apparatus has been widely observed in neurodegenerative disease. Golgi pH regulator (GPHR) is an anion channel essential for acidification of the Golgi lumen and its essential for normal morphology and function of the Golgi apparatus. To address the Golgi dysfunction in neuronal cells, we established brain-specific GPHR knockout mice (GPHRf/f;Nes).

2022-08-31 | GSE208622 | GEO

Expression data from shVDAC1 in Huh7

Project description:Our previous study has shown that the expression of voltage-dependent anion channel 1 (VDAC1) is closely related to the tumorigenesis and progression of HCC.Nevertheless, tumorigenesis and progression of HCC are complex processes, and the specific mechanism of VDAC1 affecting the proliferation and invasion of HCC has not yet been elucidated. To further study the role of downstream related molecules of VDAC1, we utilized the Affymetrix GeneChip system to analyze the downstream gene expression profile of VDAC1

2022-05-23 | GSE198538 | GEO

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