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10.1016/j.ejmech.2017.09.021

http://scihub22266oqcxt.onion/10.1016/j.ejmech.2017.09.021
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29031494!ä!29031494

suck abstract from ncbi


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pmid29031494      Eur+J+Med+Chem 2018 ; 153 (ä): 73-104
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  • NB 06: From a simple lysosomotropic aSMase inhibitor to tools for elucidating the role of lysosomes in signaling apoptosis and LPS-induced inflammation #MMPMID29031494
  • Blaess M; Bibak N; Claus RA; Kohl M; Bonaterra GA; Kinscherf R; Laufer S; Deigner HP
  • Eur J Med Chem 2018[Jun]; 153 (ä): 73-104 PMID29031494show ga
  • Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C(6)-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli-induced increase of C(16)-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis. Compounds like NB 06 thus offer highly interesting fields of application besides prevention of apoptosis of macrophages in atherosclerotic plaques in vessel walls. Most importantly, they can be used for blocking pH-dependent lysosomal processes and enzymes in general as well as for analyzing lysosomal dependent cellular signaling. Modulation of gene expression of several prominent inflammatory messengers IL1B, IL6, IL23A, CCL4 and CCL20 further indicate potentially beneficial effects in the field of (systemic) infections involving bacterial endotoxins like LPS or infections with influenza A virus.
  • |Apoptosis/*drug effects[MESH]
  • |Cell Line[MESH]
  • |Cells, Cultured[MESH]
  • |Ceramides/immunology[MESH]
  • |Enzyme Inhibitors/*chemistry/*pharmacology[MESH]
  • |Humans[MESH]
  • |Inflammation/drug therapy/immunology[MESH]
  • |Lipopolysaccharides/immunology[MESH]
  • |Lysosomes/*drug effects/immunology[MESH]
  • |Macrophages/drug effects/immunology[MESH]
  • |Signal Transduction/drug effects[MESH]


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