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U3633

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Dorothy I Mundy et al.
Molecular biology of the cell, 23(5), 864-880 (2012-01-13)
Caveolin-1 is an integral membrane protein of plasma membrane caveolae. Here we report that caveolin-1 collects at the cytosolic surface of lysosomal membranes when cells are serum starved. This is due to an elevation of the intralysosomal pH, since ionophores
Nina Raben et al.
Methods in enzymology, 453, 417-449 (2009-02-17)
Lysosomes are the final destination of the autophagic pathway. It is in the acidic milieu of the lysosomes that autophagic cargo is metabolized and recycled. One would expect that diseases with primary lysosomal defects would be among the first systems
Martina Malnar et al.
Biochimica et biophysica acta, 1822(8), 1270-1283 (2012-05-04)
Cholesterol accumulation in Niemann-Pick type C disease (NPC) causes increased levels of the amyloid-precursor-protein C-terminal fragments (APP-CTFs) and intracellular amyloid-β peptide (Aβ), the two central molecules in Alzheimer's disease (AD) pathogenesis. We previously reported that cholesterol accumulation in NPC-cells leads
Hanna Appelqvist et al.
PloS one, 7(11), e50262-e50262 (2012-11-21)
Alterations in lipid homeostasis are implicated in several neurodegenerative diseases, although the mechanisms responsible are poorly understood. We evaluated the impact of cholesterol accumulation, induced by U18666A, quinacrine or mutations in the cholesterol transporting Niemann-Pick disease type C1 (NPC1) protein
Mee Kian Poh et al.
Antiviral research, 93(1), 191-198 (2011-12-08)
The level of cholesterol in host cells has been shown to affect viral infection. However, it is still not understood why this level of regulation is important for successful infection. We have shown in this study that dengue virus infection
John J Reiners et al.
Free radical biology & medicine, 50(2), 281-294 (2010-11-16)
Reactive oxygen species (ROS) can induce lysosomal membrane permeabilization (LMP). Photoirradiation of murine hepatoma 1c1c7 cultures preloaded with the photosensitizer NPe6 generates singlet oxygen within acidic organelles and causes LMP and the activation of procaspases. Treatment with the cationic amphiphilic
Eric Cortada et al.
Journal of cell science, 134(6) (2021-02-20)
The voltage-gated sodium channel is critical for cardiomyocyte function. It consists of a protein complex comprising a pore-forming α subunit and associated β subunits. In polarized Madin-Darby canine kidney cells, we show evidence by acyl-biotin exchange that β2 is S-acylated
Matteo Da Ros et al.
Molecular and cellular endocrinology, 401, 73-83 (2014-12-09)
Spermatozoa are produced during spermatogenesis as a result of mitotic proliferation, meiosis and cellular differentiation. Postmeiotic spermatids are exceptional cells given their haploid genome and remarkable sperm-specific structural transformations to compact and reshape the nucleus and to construct the flagellum
Francesc X Guix et al.
Life science alliance, 4(8) (2021-06-30)
As neurons age, they show a decrease in their ability to degrade proteins and membranes. Because undegraded material is a source of toxic products, defects in degradation are associated with reduced cell function and survival. However, there are very few
Rui Liu et al.
Autophagy, 10(7), 1241-1255 (2014-06-07)
Glioblastoma is one of the most aggressive human cancers with poor prognosis, and therefore a critical need exists for novel therapeutic strategies for management of glioblastoma patients. Itraconazole, a traditional antifungal drug, has been identified as a novel potential anticancer
Yunash Maharjan et al.
EMBO reports, 21(5), e48901-e48901 (2020-03-12)
Recent evidence has linked the lysosomal cholesterol accumulation in Niemann-Pick type C1 with anomalies associated with primary ciliogenesis. Here, we report that perturbed intracellular cholesterol distribution imposed by lysosomal cholesterol accumulation during TMEM135 depletion is closely associated with impaired ciliogenesis.
Alexander Schneede et al.
Journal of cellular and molecular medicine, 15(2), 280-295 (2009-11-26)
The mechanisms of endosomal and lysosomal cholesterol traffic are still poorly understood. We showed previously that unesterified cholesterol accumulates in the late endosomes and lysosomes of fibroblasts deficient in both lysosome associated membrane protein-2 (LAMP-2) and LAMP-1, two abundant membrane
Jing Xu et al.
Proceedings of the National Academy of Sciences of the United States of America, 107(10), 4764-4769 (2010-02-24)
Mammalian target of rapamycin (mTOR) constitutes a nodal point of a signaling network that regulates cell growth and proliferation in response to various environmental cues ranging from growth factor stimulation to nutrients to stress. Whether mTOR is also affected by
Ke-Yong Tian et al.
Neuroscience letters, 706, 99-104 (2019-05-16)
Hearing loss is a common sensory disorder that affects more than 360 million people worldwide, and is primarily caused by the loss of hair cells (HCs). Ototoxic drugs, viral infections, genetic predisposition, aging or noise all damage HCs. 3β-hydroxysteroid-Δ24 reductase
Martijn J C van der Lienden et al.
International journal of molecular sciences, 22(5) (2021-04-04)
The lysosomal storage disease Niemann-Pick type C (NPC) is caused by impaired cholesterol efflux from lysosomes, which is accompanied by secondary lysosomal accumulation of sphingomyelin and glucosylceramide (GlcCer). Similar to Gaucher disease (GD), patients deficient in glucocerebrosidase (GCase) degrading GlcCer
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Marie-Claude Battista et al.
The Prostate, 70(9), 921-933 (2010-02-19)
Seladin-1 belongs to a subgroup of androgen-dependent genes associated with anti-proliferative, pro-differentiation, and pro-apoptotic functions and plays a protective role against oncogenic stress. The present study aims to investigate the localization and expression of Seladin-1 protein in normal and tumoral
Antonia P Gunesch et al.
Antimicrobial agents and chemotherapy, 64(8) (2020-06-10)
Several cationic amphiphilic drugs (CADs) have been found to inhibit cell entry of filoviruses and other enveloped viruses. Structurally unrelated CADs may have antiviral activity, yet the underlying common mechanism and structure-activity relationship are incompletely understood. We aimed to understand
Takashi Takano et al.
Journal of hepatology, 55(3), 512-521 (2010-12-28)
We characterized the role of 24-dehydrocholesterol reductase (DHCR24) in hepatitis C virus infection (HCV). DHCR24 is a cholesterol biosynthetic enzyme and cholesterol is a major component of lipid rafts, which is reported to play an important role in HCV replication.
Andrew S Herbert et al.
mBio, 6(3), e00565-e00515 (2015-05-28)
Recent work demonstrated that the Niemann-Pick C1 (NPC1) protein is an essential entry receptor for filoviruses. While previous studies focused on filovirus entry requirements of NPC1 in vitro, its roles in filovirus replication and pathogenesis in vivo remain unclear. Here
Thomas Pfeifer et al.
Current pharmaceutical biotechnology, 12(2), 285-292 (2010-12-31)
The liver X receptors (LXRs) are key regulators of genes involved in cholesterol homeostasis. Natural ligands and activators of LXRs are oxysterols. Numerous steroidal and non-steroidal synthetic LXR ligands are under development as potential drugs for individuals suffering from lipid
Sabine Chapuy-Regaud et al.
Biochimie, 95(9), 1677-1688 (2013-06-19)
Progesterone, the cationic amphiphile U18666A and a phospholipase inhibitor (Methyl Arachidonyl Fluoro Phosphonate, MAFP) inhibited by 70%-90% HIV production in viral reservoir cells, i.e. human THP-1 monocytes and monocyte-derived macrophages (MDM). These compounds triggered an inhibition of fluid phase endocytosis
Katrin Strauss et al.
The Journal of biological chemistry, 285(34), 26279-26288 (2010-06-18)
Niemann-Pick type C1 disease is an autosomal-recessive lysosomal storage disorder. Loss of function of the npc1 gene leads to abnormal accumulation of free cholesterol and sphingolipids within the late endosomal and lysosomal compartments resulting in progressive neurodegeneration and dysmyelination. Here
Rusella Mirza et al.
Journal of bone and mineral metabolism, 30(2), 144-153 (2011-08-17)
Desmosterolosis is an autosomal recessive disease caused by mutations in the 3β-hydroxysterol-Delta24 reductase (DHCR24) gene, with severe developmental anomalies including short limbs. We utilized DHCR24 knockout (KO) mice to study the underlying bone pathology. Because the KO mice died within
Matthew F Pescosolido et al.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 41(44), 9235-9256 (2021-09-17)
Loss-of-function mutations in endosomal Na+/H+ exchanger 6 (NHE6) cause the X-linked neurologic disorder Christianson syndrome. Patients exhibit symptoms associated with both neurodevelopmental and neurodegenerative abnormalities. While loss of NHE6 has been shown to overacidify the endosome lumen, and is associated
Alexander N Kapustin et al.
Communications biology, 4(1), 1241-1241 (2021-11-03)
Next generation modified antisense oligonucleotides (ASOs) are commercially approved new therapeutic modalities, yet poor productive uptake and endosomal entrapment in tumour cells limit their broad application. Here we compare intracellular traffic of anti KRAS antisense oligonucleotide (AZD4785) in tumour cell
Blair R Roszell et al.
American journal of physiology. Lung cellular and molecular physiology, 302(9), L919-L932 (2012-03-01)
The Niemann-Pick C (NPC) pathway plays an essential role in the intracellular trafficking of cholesterol by facilitating the release of lipoprotein-derived sterol from the lumen of lysosomes. Regulation of cellular cholesterol homeostasis is of particular importance to lung alveolar type
Néstor Más Gómez et al.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 32(2), 782-794 (2017-10-17)
The transient receptor potential cation channel mucolipin 1 (TRPML1) channel is a conduit for lysosomal calcium efflux, and channel activity may be affected by lysosomal contents. The lysosomes of retinal pigmented epithelial (RPE) cells are particularly susceptible to build-up of
Hiroyuki Nakamura et al.
Journal of cellular physiology, 227(7), 2847-2855 (2011-09-20)
Niemann-Pick disease type C (NPC) is a neurodegenerative lipid storage disorder caused by mutations in NPC1 or NPC2 genes. Loss of function of either protein results in the endosomal accumulation of cholesterol and other lipids. Here, we report that NPC1-deficient
Sang Y Lee et al.
Anticancer research, 41(6), 2795-2804 (2021-06-05)
Neuroblastoma is the most common childhood extracranial solid malignancy. Although cancer cells need iron and lipids for active cell division, possible links between iron and lipid metabolism in neuroblastomas have not been studied. We evaluated the levels and association between
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