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LPS induces pulmonary microvascular endothelial cell barrier dysfunction by upregulating ceramide production
Cell Signal. 2022 Jan 19:110250. doi: 10.1016/j.cellsig.2022.110250. Online ahead of print.ABSTRACTThe specific role of ceramides in pulmonary microvascular endothelial cell (PMVEC) barrier dysfunction remains unclear. In the present study, pretreatment with pan-caspase inhibitors significantly reduced LPS-induced PMVEC apoptosis and helped to stimulate PMVEC barrier reconstruction after 12 h but had no effect on PMVEC barrier dysfunction in the first 8 h. Further studies showed that imipramine, an acid sphingomyelinase (ASMase) inhibitor, significantly inhibited LPS-induced barrier dysfunction, while an siRNA targeting se...
Source: Cellular Signalling - January 22, 2022 Category: Cytology Authors: Jianjun Jiang Huijuan Ouyang Qun Zhou Sihui Tang Pu Fang Guofang Xie Jin Yang Gengyun Sun Source Type: research

Aging-Dependent Downregulation of SUV39H1 Histone Methyltransferase Increases Susceptibility to Stress-Induced Depressive Behavior
AbstractAging induces cellular and molecular changes including gene expression alteration in the brain, which might be associated with aging-induced decrease in stress coping ability. In the present study, we investigate how aging changes the ability to cope with stress and increases sensitivity to stress. Aged mice show decreased expression of SUV39H1 histone methyltransferase and increased expression of Mkp-1 in the hippocampus. The siRNA-mediated knockdown of SUV39H1 increases Mkp-1 expression and suppresses p-CREB and Bdnf expression in HT22 cells and in the hippocampus of mice. Chromatin immunoprecipitation assays ind...
Source: Molecular Neurobiology - September 18, 2021 Category: Neurology Source Type: research

Enhancement of Liposomal Plasmid DNA and siRNA Delivery by Itraconazole through Intracellular Cholesterol Accumulation
ConclusionsItraconazole enhanced gene delivery of pDNA and siRNA, and it can be used to potentiate nucleic acid therapeutics.
Source: Pharmaceutical Research - June 10, 2020 Category: Drugs & Pharmacology Source Type: research

Cellular uptake properties of lamotrigine in human placental cell lines: Investigation of involvement of organic cation transporters (SLC22A1-5).
Authors: Hasegawa N, Furugen A, Ono K, Koishikawa M, Miyazawa Y, Nishimura A, Umazume T, Narumi K, Kobayashi M, Iseki K Abstract Lamotrigine (LTG) is an important antiepileptic drug for the treatment of seizures in pregnant women with epilepsy. However, it is not known if the transport of LTG into placental cells occurs via a carrier-mediated pathway. The aim of this study was to investigate the uptake properties of LTG into placental cell lines (BeWo and JEG-3), and to determine the involvement of organic cation transporters (OCTs, SLC22A1-3) and organic cation/carnitine transporter (OCTNs, SLC22A4-5) in the uptak...
Source: Drug Metabolism and Pharmacokinetics - April 20, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Pharmacokinet Source Type: research

Inhibition of acid sphingomyelinase disrupts LYNUS signaling and triggers autophagy Research Articles
Activation of the lysosomal ceramide-producing enzyme, acid sphingomyelinase (ASM), by various stresses is centrally involved in cell death and has been implicated in autophagy. We set out to investigate the role of the baseline ASM activity in maintaining physiological functions of lysosomes, focusing on the lysosomal nutrient-sensing complex (LYNUS), a lysosomal membrane-anchored multiprotein complex that includes mammalian target of rapamycin (mTOR) and transcription factor EB (TFEB). ASM inhibition with imipramine or sphingomyelin phosphodiesterase 1 (SMPD1) siRNA in human lung cells, or by transgenic Smpd1+/– ha...
Source: The Journal of Lipid Research - April 1, 2018 Category: Lipidology Authors: Justice, M. J., Bronova, I., Schweitzer, K. S., Poirier, C., Blum, J. S., Berdyshev, E. V., Petrache, I. Tags: Research Articles Source Type: research

Increased Signaling via Adenosine A1 Receptors, Sleep Deprivation, Imipramine, and Ketamine Inhibit Depressive-like Behavior via Induction of Homer1a
Publication date: 5 August 2015 Source:Neuron, Volume 87, Issue 3 Author(s): Tsvetan Serchov, Hans-Willi Clement, Martin K. Schwarz, Felice Iasevoli, Dilip K. Tosh, Marco Idzko, Kenneth A. Jacobson, Andrea de Bartolomeis, Claus Normann, Knut Biber, Dietrich van Calker Major depressive disorder is among the most commonly diagnosed disabling mental diseases. Several non-pharmacological treatments of depression upregulate adenosine concentration and/or adenosine A1 receptors (A1R) in the brain. To test whether enhanced A1R signaling mediates antidepressant effects, we generated a transgenic mouse with enhanc...
Source: Neuron - August 6, 2015 Category: Neuroscience Source Type: research

Tissue transglutaminase promotes serotonin-induced AKT signaling and mitogenesis in pulmonary vascular smooth muscle cells.
Abstract Tissue transglutaminase 2 (TG2) is a multifunctional enzyme that cross-links proteins with monoamines such as serotonin (5-hydroxytryptamine, 5-HT) via a transglutamidation reaction, and is associated with pathophysiologic vascular responses. 5-HT is a mitogen for pulmonary artery smooth muscle cells (PASMCs) that has been linked to pulmonary vascular remodeling underlying pulmonary hypertension development. We previously reported that 5-HT-induced PASMC proliferation is inhibited by the TG2 inhibitor monodansylcadaverine (MDC); however, the mechanisms are poorly understood. In the present study we hypoth...
Source: Cellular Signalling - September 9, 2014 Category: Cytology Authors: Penumatsa K, Abualkhair S, Wei L, Warburton R, Preston I, Hill NS, Watts SW, Fanburg BL, Toksoz D Tags: Cell Signal Source Type: research