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Articles de revues sur le sujet « Agent lysosomotrope »

Auteur : Grafiati

Publié le 4 juin 2021

Mis à jour le 12 février 2022

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1

Firestone, Raymond A., Judith M. Pisano, George M. Garrity, Robert A. Fromtling, and Sheldon B. Zimmerman. "Lysosomotropic agents. 7. Broad-spectrum antifungal activity of lysosomotropic detergents." Journal of Medicinal Chemistry 30, no. 8 (1987): 1519–21. http://dx.doi.org/10.1021/jm00391a043.

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2

MIR, MUDASIR. "LYSOSOMOTROPIC PROPERTIES OF SODIUM BICARBONATE AND COVID-19." FARMACIA 68, no. 5 (2020): 771–78. http://dx.doi.org/10.31925/farmacia.2020.5.1.

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SARS-CoV-2 causing COVID-19 has appeared as an ongoing global public crisis, growing with geometric progression and has caused huge devastation till date majorly because of lack of targeted therapeutic agents like vaccines. SARS-Cov-2 entrance into the host cells is reliant on acidic pH. Thus, in the current clinical emergency there is a pressing need to look forward for adjunct therapies which could counter the acidic pH, so as to restrain the viral entry and its subsequent reproduction in the host cells. Therefore, the current review attempted to explore the possibility to use sodium bicarbo

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3

Kalina, M., and R. Socher. "Endocytosis in cultured rat alveolar type II cells: effect of lysosomotropic weak bases on the processes." Journal of Histochemistry & Cytochemistry 39, no. 10 (1991): 1337–48. http://dx.doi.org/10.1177/39.10.1658127.

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We investigated the uptake of Lucifer yellow and surfactant complexed with gold (S-G) by isolated alveolar Type II cells. The fluid phase marker Lucifer yellow did not reach lamellar bodies (LB) even after prolonged incubation time, whereas S-G was internalized and found in LB. Treatment of Type II cells with lysosomotropic weak bases (NH4Cl and chloroquine) resulted in dilation of endosomes, lysosomes, and LB. The effect of these agents on LB resulted in disappearance of their lamellar organization, as detected by polarized light and electron microscopy. After incubation in lysosomotropic age

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4

Villamil Giraldo, Ana M., Hanna Appelqvist, Thomas Ederth, and Karin Öllinger. "Lysosomotropic agents: impact on lysosomal membrane permeabilization and cell death." Biochemical Society Transactions 42, no. 5 (2014): 1460–64. http://dx.doi.org/10.1042/bst20140145.

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Lysosomes are acidic organelles essential for degradation, signalling and cell homoeostasis. In addition, they play a key role in cell death. Permeabilization of the lysosomal membrane and release of hydrolytic enzymes to the cytosol accompanies apoptosis signalling in several systems. The regulatory mechanism of lysosomal stability is, however, poorly understood. Lipophilic or amphiphilic compounds with a basic moiety will become protonated and trapped within lysosomes, and such lysosomotropic behaviour is also found in many pharmacological drugs. The natural sphingolipid sphingosine exhibits

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5

Chen, Grace L., Sarah L. Sutrina, Karen L. Frayer, and Winston W. Chen. "Effects of lysosomotropic agents on lipogenesis." Archives of Biochemistry and Biophysics 245, no. 1 (1986): 66–75. http://dx.doi.org/10.1016/0003-9861(86)90190-6.

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Xiong, Subin, Hong Li, Bo Yu, Jun Wu, and Robert J. Lee. "Triggering Liposomal Drug Release With a Lysosomotropic Agent." Journal of Pharmaceutical Sciences 99, no. 12 (2010): 5011–18. http://dx.doi.org/10.1002/jps.22210.

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7

Doi, Syuichi, Kazuyuku Tanabe, Masayasu Watanabe, and Masao Yoshimura. "Chloroquine, a lysosomotropic agent, inhibits zygote formation in yeast." Archives of Microbiology 151, no. 1 (1988): 20–25. http://dx.doi.org/10.1007/bf00444663.

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Liu, Zhenxing, Shuan Zhao, Shuaishuai Wu, Jingyou Zhang, Zunyang Nie, and Shenming Zeng. "A novel role of transient receptor potential mucolipin1 (TRPML1) in protecting against imidazole-induced cytotoxicity." Biochemistry and Cell Biology 92, no. 4 (2014): 279–86. http://dx.doi.org/10.1139/bcb-2014-0044.

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Lysosomotropic amines cause serious side effects such as cytoplasmic vacuolation and cell death. TRPML1 (also known as mucolipin1), a member of the transient receptor potential (TRP) protein family, may regulate fusion/fission of vesicles along the endocytic pathway and some aspects of lysosomal ion homeostasis. Nevertheless, it is still unknown whether TRPML1 is involved in death of mammalian cells induced by lysosomotropic agents. In this study, imidazole was used as a model to investigate the role of TRPML1 in the cytotoxicity of lysosomotropic agents. Overexpression of wild-type TRPML1 inh

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9

SHAMSADEEN, NASRIN, and C. J. DUNCAN. "Action of lysosomotropic agents on mammalian skeletal muscle." Biochemical Society Transactions 16, no. 5 (1988): 786. http://dx.doi.org/10.1042/bst0160786.

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10

Duncan, R. "Designing polymer conjugates as lysosomotropic nanomedicines." Biochemical Society Transactions 35, no. 1 (2007): 56–60. http://dx.doi.org/10.1042/bst0350056.

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Marriage of cell biology (the concept of ‘lysosomotropic drug delivery’) and the realization that water-soluble synthetic polymers might provide an ideal platform for targeted drug delivery led to the first synthetic polymer–drug conjugates that entered clinical trials as anticancer agents. Conceptually, polymer conjugates share many features with other macromolecular drugs, but they have the added advantage of the versatility of synthetic chemistry that allows tailoring of molecular mass and addition of biomimetic features. Conjugate characteristics must be optimized carefully to ensure that

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11

Korolenko, Tatiana A., Thomas P. Johnston, and Vaclav Vetvicka. "Lysosomotropic Features and Autophagy Modulators among Medical Drugs: Evaluation of Their Role in Pathologies." Molecules 25, no. 21 (2020): 5052. http://dx.doi.org/10.3390/molecules25215052.

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The concept of lysosomotropic agents significantly changed numerous aspects of cellular biochemistry, biochemical pharmacology, and clinical medicine. In the present review, we focused on numerous low-molecular and high-molecular lipophilic basic compounds and on the role of lipophagy and autophagy in experimental and clinical medicine. Attention was primarily focused on the most promising agents acting as autophagy inducers, which offer a new window for treatment and/or prophylaxis of various diseases, including type 2 diabetes mellitus, Parkinson’s disease, and atherosclerosis. The present r

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12

Niemann, Axel, Akira Takatsuki, and Hans-Peter Elsässer. "The Lysosomotropic Agent Monodansylcadaverine Also Acts as a Solvent Polarity Probe." Journal of Histochemistry & Cytochemistry 48, no. 2 (2000): 251–58. http://dx.doi.org/10.1177/002215540004800210.

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The autofluorescent substance monodansylcadaverine has recently been reported as a specific in vivo marker for autophagic vacuoles. However, the mechanism for this specific labeling remained unclear. Our results reveal that the common model of ion trapping in acidic compartments cannot completely account for the observed autophagic vacuole staining. Because autophagic vacuoles are characterized by myelin-like membrane inclusions, we tested whether this lipid-rich environment is responsible for the staining properties of monodansylcadaverine. In in vitro experiments using either liposomes or so

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13

Zou, Xiaoqian, Fei Meng, Chengyu Fu, et al. "LZ-106, a potent lysosomotropic agent, causing TFEB-dependent cytoplasmic vacuolization." Gene 760 (November 2020): 145017. http://dx.doi.org/10.1016/j.gene.2020.145017.

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Hagforsen, Eva, Aida Paivandy, Maria Lampinen, et al. "Ablation of human skin mast cellsin situby lysosomotropic agents." Experimental Dermatology 24, no. 7 (2015): 516–21. http://dx.doi.org/10.1111/exd.12699.

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15

Zeman, R. J., P. L. Bernstein, R. Ludemann, and J. D. Etlinger. "Regulation of Ca2+-dependent protein turnover in skeletal muscle by thyroxine." Biochemical Journal 240, no. 1 (1986): 269–72. http://dx.doi.org/10.1042/bj2400269.

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Dantrolene, an agent that inhibits Ca2+ mobilization, improved protein balance in skeletal muscle, as thyroid status was increased, by altering rates of protein synthesis and degradation. Thyroxine (T4) caused increases in protein degradation that were blocked by leupeptin, a proteinase inhibitor previously shown to inhibit Ca2+-dependent non-lysosomal proteolysis in these muscles. In addition, T4 abolished sensitivity to the lysosomotropic agent methylamine and the autophagy inhibitor 3-methyladenine, suggesting that T4 inhibits autophagic/lysosomal proteolysis.

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Shaikh, Soni, Suman K. Nandy, Carles Cantí, and Sergio Lavandero. "Bafilomycin-A1 and ML9 Exert Different Lysosomal Actions to Induce Cell Death." Current Molecular Pharmacology 12, no. 4 (2019): 261–71. http://dx.doi.org/10.2174/1874467212666190308131250.

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Objective: Bafilomycin-A1 and ML9 are lysosomotropic agents, irrespective of cell types. However, the mechanisms of lysosome targeting either bafilomycin-A1 or ML9 are unclear. Methods: The present research has been carried out by different molecular and biochemical analyses like western blot, confocal imaging and FACS studies, as well as molecular docking. Results: Our data shows that pre-incubation of neonatal cardiomyocytes with ML9 for 4h induced cell death, whereas a longer period of time (24h) with bafilomycin-A1 was required to induce an equivalent effect. Neither changes in ROS nor ATP

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17

Hirano, T., A. Saluja, P. Ramarao, M. M. Lerch, and M. L. Steer. "Effects of chloroquine and methylamine on lysosomal enzyme secretion by rat pancreas." American Journal of Physiology-Gastrointestinal and Liver Physiology 262, no. 3 (1992): G439—G444. http://dx.doi.org/10.1152/ajpgi.1992.262.3.g439.

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In vivo pancreatic secretion of the lysosomal hydrolase cathepsin B was found to be increased by infusion of the secretagogue caerulein. The basal as well as caerulein-stimulated in vivo rate of cathepsin B was further increased by infusion of either chloroquine or methylamine while neither the basal nor the secretagogue-stimulated rates of amylase secretion were altered by the lysosomotropic agents. These observations indicate that neutralization of the acidic prelysosomal compartment by administration of lysosomotropic agents results in lysosomal enzyme entry, by default, into the regulated

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18

Diaz-Griffero, Felipe, Steven Ari Hoschander, and Jürgen Brojatsch. "Endocytosis Is a Critical Step in Entry of Subgroup B Avian Leukosis Viruses." Journal of Virology 76, no. 24 (2002): 12866–76. http://dx.doi.org/10.1128/jvi.76.24.12866-12876.2002.

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ABSTRACT The avian leukosis virus (ALV) entry mechanism is controversial, with evidence for and against a low-pH requirement for viral fusion. To further address this question, we tested the entry of human immunodeficiency virus type 1 (HIV-1) pseudotyped with the envelope protein of subgroup B ALV (ALV-B) in the presence of three different lysosomotropic agents. These lysosomotropic agents were able to block the entry of wild-type and pseudotyped ALV-B in two different cell lines, strongly suggesting that ALV-B requires a low-pH step for entry. ALV-B and pH-dependent Semliki Forest virus (SFV

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19

Miura, Kazuki, Sayaka Kawano, Takahiro Suto, Takaaki Sato, Noritaka Chida, and Siro Simizu. "Identification of madangamine A as a novel lysosomotropic agent to inhibit autophagy." Bioorganic & Medicinal Chemistry 34 (March 2021): 116041. http://dx.doi.org/10.1016/j.bmc.2021.116041.

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Ciftci, Kadriye, and Robert J. Levy. "Enhanced plasmid DNA transfection with lysosomotropic agents in cultured fibroblasts." International Journal of Pharmaceutics 218, no. 1-2 (2001): 81–92. http://dx.doi.org/10.1016/s0378-5173(01)00623-8.

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21

Kuwahara, Tomoki, Kai Funakawa, Tadayuki Komori, et al. "Roles of lysosomotropic agents on LRRK2 activation and Rab10 phosphorylation." Neurobiology of Disease 145 (November 2020): 105081. http://dx.doi.org/10.1016/j.nbd.2020.105081.

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22

BARON, P., E. SCARPINI, G. MEOLA, M. MOGGIO, G. PELLEGRINI, and G. SCARLATO. "Morphological changes in cultured human muscle treated with lysosomotropic agents." Cell Biology International Reports 10, no. 3 (1986): 212. http://dx.doi.org/10.1016/s0309-1651(86)80066-2.

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23

Offensperger, Wolf-Bernhard, Silke Offensperger, Eike Walter, Hubert E. Blum, and Wolfgang Gerok. "Inhibition of duck hepatitis B virus infection by lysosomotropic agents." Virology 183, no. 1 (1991): 415–18. http://dx.doi.org/10.1016/0042-6822(91)90157-7.

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24

Shiraishi, Norio, Shin-Ichi Akiyama, Michio Kobayashi, and Michihiko Kuwano. "Lysosomotropic agents reverse multiple drug resistance in human cancer cells." Cancer Letters 30, no. 3 (1986): 251–59. http://dx.doi.org/10.1016/0304-3835(86)90049-2.

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25

De Lisle, R. C., and J. A. Williams. "Zymogen granule acidity is not required for stimulated pancreatic protein secretion." American Journal of Physiology-Gastrointestinal and Liver Physiology 253, no. 6 (1987): G711—G719. http://dx.doi.org/10.1152/ajpgi.1987.253.6.g711.

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It has been demonstrated recently by acridine orange fluorescence that pancreatic zymogen granules are acidic in situ, with respect to the cytoplasm. To evaluate the relationship between the acidic intragranular pH and hormone-stimulated secretion, mouse pancreatic acini were treated with lysosomotropic agents to collapse the zymogen granule pH gradient. Methylamine, monensin, and chloroquine collapsed the granule pH gradient as evidenced by a disappearance of acridine orange fluorescence. Cholecystokinin octapeptide (CCK-8)-stimulated acinar amylase secretion was unaffected in the presence of

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Lammers, G., та J. C. Jamieson. "Studies on the effect of lysosomotropic agents on the release of Gal β 1-4GlcNAc α-2,6-sialytransferase from rat liver slices during the acute-phase response". Biochemical Journal 261, № 2 (1989): 389–93. http://dx.doi.org/10.1042/bj2610389.

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The mechanism of release of Gal beta 1-4GlcNAc alpha-2,6-sialyltransferase (CMP-N-acetylneuraminate: beta-galactoside alpha-2,6-sialytransferase, EC 2.4.99.1) from rat liver during the acute-phase response is due to the action of a cathepsin D-like proteinase that cleaves the trans-Golgi membrane-bound enzyme from a membrane anchor; this allows a major portion of the enzyme containing the catalytic site to escape into the extracellular space [Lammers & Jamieson (1988) Biochem. J. 256, 623-631]. The release of sialytransferase was most effective at pH 5.6, suggesting that release of sialylt

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Kondratskyi, A., M. Yassine, C. Slomianny, et al. "Identification of ML-9 as a lysosomotropic agent targeting autophagy and cell death." Cell Death & Disease 5, no. 4 (2014): e1193-e1193. http://dx.doi.org/10.1038/cddis.2014.156.

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Ostenfeld, Marie Stampe, Maria Høyer-Hansen, Lone Bastholm, et al. "Anti-cancer agent siramesine is a lysosomotropic detergent that induces cytoprotective autophagosome accumulation." Autophagy 4, no. 4 (2008): 487–99. http://dx.doi.org/10.4161/auto.5774.

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Zeilhofer, H. U., J. Mollenhauer, and K. Brune. "Selective growth inhibition of ductal pancreatic adenocarcinoma cells by the lysosomotropic agent chloroquine." Cancer Letters 44, no. 1 (1989): 61–66. http://dx.doi.org/10.1016/0304-3835(89)90109-2.

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Hurwitz, Selwyn J., Masanori Terashima, Nobuyuki Mizunuma, and Christopher A. Slapak. "Vesicular Anthracycline Accumulation in Doxorubicin-Selected U-937 Cells: Participation of Lysosomes." Blood 89, no. 10 (1997): 3745–54. http://dx.doi.org/10.1182/blood.v89.10.3745.

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Abstract The U-A10 cell line, a doxorubicin-selected variant of human U-937 myeloid leukemia cells, exhibits a redistribution of anthracyclines into a expanded vesicular compartment. The acidic nature of this compartment was confirmed by vital staining with a pH sensitive dye, LysoSensor yellow/blue DND-160. Identification of the vesicular compartment was performed by immunofluorescence analysis. Staining for the LAMP-1 and LAMP-2 antigens showed that the vesicles are enlarged lysosomes that are eccentrically placed near the nucleus of U-A10 cells. By contrast, the expression of the multidrug

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Hurwitz, Selwyn J., Masanori Terashima, Nobuyuki Mizunuma, and Christopher A. Slapak. "Vesicular Anthracycline Accumulation in Doxorubicin-Selected U-937 Cells: Participation of Lysosomes." Blood 89, no. 10 (1997): 3745–54. http://dx.doi.org/10.1182/blood.v89.10.3745.3745_3745_3754.

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The U-A10 cell line, a doxorubicin-selected variant of human U-937 myeloid leukemia cells, exhibits a redistribution of anthracyclines into a expanded vesicular compartment. The acidic nature of this compartment was confirmed by vital staining with a pH sensitive dye, LysoSensor yellow/blue DND-160. Identification of the vesicular compartment was performed by immunofluorescence analysis. Staining for the LAMP-1 and LAMP-2 antigens showed that the vesicles are enlarged lysosomes that are eccentrically placed near the nucleus of U-A10 cells. By contrast, the expression of the multidrug resistanc

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Fantus, I. G., R. George, S. Tang, P. Chong, and M. J. Poznansky. "The Insulin-Mimetic Agent Vanadate Promotes Receptor Endocytosis and Inhibits Intracellular Ligand-Receptor Degradation by a Mechanism Distinct From the Lysosomotropic Agents." Diabetes 45, no. 8 (1996): 1084–93. http://dx.doi.org/10.2337/diab.45.8.1084.

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Fantus, I. G., R. George, S. Tang, P. Chong, and M. J. Poznansky. "The insulin-mimetic agent vanadate promotes receptor endocytosis and inhibits intracellular ligand-receptor degradation by a mechanism distinct from the lysosomotropic agents." Diabetes 45, no. 8 (1996): 1084–93. http://dx.doi.org/10.2337/diabetes.45.8.1084.

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Van Oost, B. A., J. B. Smith, H. Holmsen, and G. D. Vladutiu. "Lysosomotropic agents selectively potentiate thrombin-induced acid hydrolase secretion from platelets." Proceedings of the National Academy of Sciences 82, no. 8 (1985): 2374–78. http://dx.doi.org/10.1073/pnas.82.8.2374.

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Domagala, Antoni, Malgorzata Bobrowicz, Joanna Stachura, et al. "Lysosomal Disruption Augments Obinutuzumab-Induced Direct Cell Death." Blood 128, no. 22 (2016): 2766. http://dx.doi.org/10.1182/blood.v128.22.2766.2766.

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Abstract Anti-CD20 mononclonal antibodies (mAbs) have a well-established role in the treatment of B-cell lymphoid malignancies. In addition to classic Fc-dependent mechanisms, including antibody-dependent and complement-mediated cytotoxicity, the so-called type II mAbs induce direct cell death. It has been shown that obinutuzumab, without Fc-crosslinking agents or effector cells, triggers non-apoptotic, lysosomal-dependent programmed cell death (PCD). The mechanism of PCD is characterized by actin reorganization, followed by permeabilization of the lysosomal membrane and subsequent generation

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Shamsadeen, N., and C. J. Duncan. "Cytotoxic action of the lysosomotropic agent L-leucine methyl ester on mammalian skeletal muscle." Virchows Archiv B Cell Pathology Including Molecular Pathology 57, no. 1 (1989): 315–21. http://dx.doi.org/10.1007/bf02899096.

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Villalpando-Rodriguez, Gloria E., Anna R. Blankstein, Carmen Konzelman, and Spencer B. Gibson. "Lysosomal Destabilizing Drug Siramesine and the Dual Tyrosine Kinase Inhibitor Lapatinib Induce a Synergistic Ferroptosis through Reduced Heme Oxygenase-1 (HO-1) Levels." Oxidative Medicine and Cellular Longevity 2019 (September 17, 2019): 1–14. http://dx.doi.org/10.1155/2019/9561281.

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Ferroptosis is an iron-dependent type of cell death distinct from apoptosis or necrosis characterized by accumulation of reactive oxygen species. The combination of siramesine, a lysosomotropic agent, and lapatinib, a dual tyrosine kinase inhibitor (TKI), synergistically induced cell death in breast cancer cells mediated by ferroptosis. In this study, we showed that this combination of siramesine and lapatinib induces synergistic cell death in glioma cell line U87 and lung adenocarcinoma cell line A549. This cell death was characterized by the increase in iron content, reactive oxygen species

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Doh-ura, K., T. Iwaki, and B. Caughey. "Lysosomotropic Agents and Cysteine Protease Inhibitors Inhibit Scrapie-Associated Prion Protein Accumulation." Journal of Virology 74, no. 10 (2000): 4894–97. http://dx.doi.org/10.1128/jvi.74.10.4894-4897.2000.

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Degtyarev, Michael, Ann De Mazière, Christine Orr, et al. "Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents." Journal of Cell Biology 183, no. 1 (2008): 101–16. http://dx.doi.org/10.1083/jcb.200801099.

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Although Akt is known as a survival kinase, inhibitors of the phosphatidylinositol 3-kinase (PI3K)–Akt pathway do not always induce substantial apoptosis. We show that silencing Akt1 alone, or any combination of Akt isoforms, can suppress the growth of tumors established from phosphatase and tensin homologue–null human cancer cells. Although these findings indicate that Akt is essential for tumor maintenance, most tumors eventually rebound. Akt knockdown or inactivation with small molecule inhibitors did not induce significant apoptosis but rather markedly increased autophagy. Further treatmen

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Chengula, Augustino Alfred, Stephen Mutoloki, Øystein Evensen, and Hetron Mweemba Munang’andu. "Tilapia Lake Virus Does Not Hemagglutinate Avian and Piscine Erythrocytes and NH4Cl Does Not Inhibit Viral Replication In Vitro." Viruses 11, no. 12 (2019): 1152. http://dx.doi.org/10.3390/v11121152.

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Tilapia lake virus (TiLV) is a negative-sense single-stranded RNA (-ssRNA) icosahedral virus classified to be the only member in the family Amnoonviridae. Although TiLV segment-1 shares homology with the influenza C virus PB1 and has four conserved motifs similar to influenza A, B, and C polymerases, it is unknown whether there are other properties shared between TiLV and orthomyxovirus. In the present study, we wanted to determine whether TiLV agglutinated avian and piscine erythrocytes, and whether its replication was inhibited by lysosomotropic agents, such as ammonium chloride (NH4Cl), as

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Gores, G. J., L. J. Miller, and N. F. LaRusso. "Hepatic processing of cholecystokinin peptides. II. Cellular metabolism, transport, and biliary excretion." American Journal of Physiology-Gastrointestinal and Liver Physiology 250, no. 3 (1986): G350—G356. http://dx.doi.org/10.1152/ajpgi.1986.250.3.g350.

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We have shown that radiolabeled cholecystokinin octapeptide (CCK-8), CCK-8-desulfate, and CCK-4 are extracted by the liver in a structurally specific manner. Thus, we studied the fate of the extracted radiolabeled peptides by quantitating biliary excretion and determining the nature of the metabolites in bile. There was rapid biliary excretion of labeled CCK-8, CCK-8-desulfate, and CCK-4 by the isolated, perfused rat liver; greater than 75% of the extracted dose and greater than 20% of the injected dose appeared in bile within 20 min after a single pass across the liver. By means of high-perfo

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Niemann, Axel, Jennifer Baltes, and Hans-Peter Elsässer. "Fluorescence Properties and Staining Behavior of Monodansylpentane, a Structural Homologue of the Lysosomotropic Agent Monodansylcadaverine." Journal of Histochemistry & Cytochemistry 49, no. 2 (2001): 177–85. http://dx.doi.org/10.1177/002215540104900205.

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OUAR, Zahia, Marcelle BENS, Caroline VIGNES, et al. "Inhibitors of vacuolar H+-ATPase impair the preferential accumulation of daunomycin in lysosomes and reverse the resistance to anthracyclines in drug-resistant renal epithelial cells." Biochemical Journal 370, no. 1 (2003): 185–93. http://dx.doi.org/10.1042/bj20021411.

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It has been suggested that the inappropriate sequestration of weak-base chemotherapeutic drugs in acidic vesicles by multidrug-resistance (MDR) cells contributes to the mechanisms of drug resistance. The function of the acidic lysosomes can be altered in MDR cells, and so we investigated the effects of lysosomotropic agents on the secretion of lysosomal enzymes and on the intracellular distribution of the weak-base anthracycline daunomycin in drug-resistant renal proximal tubule PKSV-PRcol50 cells and their drug-sensitive PKSV-PR cell counterparts. Imaging studies using pH-dependent lysosomotr

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Bestion, Eloïne, Zuzana Macek Jilkova, Jean-Louis Mège та ін. "GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-β1 inhibition". Therapeutic Advances in Chronic Disease 11 (січень 2020): 204062232094204. http://dx.doi.org/10.1177/2040622320942042.

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Background: Hepatic fibrosis is the result of chronic liver injury that can progress to cirrhosis and lead to liver failure. Nevertheless, there are no anti-fibrotic drugs licensed for human use. Here, we investigated the anti-fibrotic activity of GNS561, a new lysosomotropic molecule with high liver tropism. Methods: The anti-fibrotic effect of GNS561 was determined in vitro using LX-2 hepatic stellate cells (HSCs) and primary human HSCs by studying cell viability, activity of caspases 3/7, autophagic flux, cathepsin maturation and activity, HSC activation and transforming growth factor-β1 (T

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A. Marinelli, Raúl, and Guillermo L. Pen̄alva. "Effect of lysosomotropic agents on the taurocholate-stimulated biliary excretion of horseradish peroxidase." Biochemical Pharmacology 44, no. 8 (1992): 1683–86. http://dx.doi.org/10.1016/0006-2952(92)90488-5.

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Ndolo, Rosemary A., Yepeng Luan, Shaofeng Duan, M. Laird Forrest, and Jeffrey P. Krise. "Lysosomotropic Properties of Weakly Basic Anticancer Agents Promote Cancer Cell Selectivity In Vitro." PLoS ONE 7, no. 11 (2012): e49366. http://dx.doi.org/10.1371/journal.pone.0049366.

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Wernersson, S., M. Riihimäki, G. Pejler, and I. Waern. "Equine Airway Mast Cells are Sensitive to Cell Death Induced by Lysosomotropic Agents." Scandinavian Journal of Immunology 85, no. 1 (2017): 30–34. http://dx.doi.org/10.1111/sji.12502.

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Dielschneider, R. F., H. Eisenstat, S. Mi, et al. "Lysosomotropic agents selectively target chronic lymphocytic leukemia cells due to altered sphingolipid metabolism." Leukemia 30, no. 6 (2016): 1290–300. http://dx.doi.org/10.1038/leu.2016.4.

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Eng, Christina H., Zuncai Wang, Diane Tkach, et al. "Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy." Proceedings of the National Academy of Sciences 113, no. 1 (2015): 182–87. http://dx.doi.org/10.1073/pnas.1515617113.

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Macroautophagy is a key stress-response pathway that can suppress or promote tumorigenesis depending on the cellular context. Notably, Kirsten rat sarcoma (KRAS)-driven tumors have been reported to rely on macroautophagy for growth and survival, suggesting a potential therapeutic approach of using autophagy inhibitors based on genetic stratification. In this study, we evaluated whether KRAS mutation status can predict the efficacy to macroautophagy inhibition. By profiling 47 cell lines with pharmacological and genetic loss-of-function tools, we were unable to confirm that KRAS-driven tumor li

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Chu, J. J. H., and M. L. Ng. "Infectious Entry of West Nile Virus Occurs through a Clathrin-Mediated Endocytic Pathway." Journal of Virology 78, no. 19 (2004): 10543–55. http://dx.doi.org/10.1128/jvi.78.19.10543-10555.2004.

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ABSTRACT The pathway of West Nile flavivirus early internalization events was mapped in detail in this study. Overexpression of dominant-negative mutants of Eps15 strongly inhibits West Nile virus (WNV) internalization, and pharmacological drugs that blocks clathrin also caused a marked reduction in virus entry but not caveola-dependent endocytosis inhibitory agent, filipin. Using immunocryoelectron microscopy, WNV particles were seen within clathrin-coated pits after 2 min postinfection. Double-labeling immunofluorescence assays and immunoelectron microscopy performed with anti-WNV envelope o

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