Chloroquine lysosomal degradation

Discussion in 'Chloroquine Phosphate' started by marik550, 05-Mar-2020.

  1. xheiko User

    Chloroquine lysosomal degradation


    In MDA-MB-231 cells, immunolocalization and brefeldin A protein transport blocking studies revealed that there was a propensity for newly synthesized Cx43 to be transported to lysosomes. On the other hand, light and electron microscopic analysis of BICR-M1R cells showed that Cx43 gap junctions were prevalent with a subpopulation of intracellular Cx43 localized to lysosomes.

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    Role of Autophagy in Glycogen Breakdown and Its Relevance to Chloroquine Myopathy Jonathan Zirin1*, Joppe Nieuwenhuis1, Norbert Perrimon1,2* 1Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, 2Howard Hughes Medical Institute, Harvard Medical School, Boston, Lysosomal origin lysosomal lipase, LAL, EC 3.1.1.13. Its involvement in endogenous TAG degradation was first demonstrated by Debeer et al. 1979 who showed on isolated hepatocytes that lysosomotropic agents chloroquine or NH4Cl that inactivate lysosomal enzymes via elevation of intralysosomal pH However, the full extent of CQ pharmacology in humans is still unclear. Herein, we demonstrate that the lysosomal protein saposin B sapB, critical for select lipid degradation, binds CQ with implications for both CQ function and toxicity.

    Interestingly, lactacystin inhibition of proteosomal degradation in MDA-MB-231 cells resulted in a marked increase in phosphorylated Cx43 at the expense of non-phosphorylated Cx43, and this change corresponded with an increase in “oversized” gap junction plaques. In both cell types, Western blots revealed a notable increase in total cellular Cx43 in response to lysosome inhibitors.

    Chloroquine lysosomal degradation

    CST - Chloroquine, Autophagy-Lysosomal Pathway Is Involved in Lipid Degradation.

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  6. Several lysosomal inhibitors such as bafilomycin A1 BafA1, protease inhibitors and chloroquine CQ, have been used interchangeably to block autophagy in in vitro experiments assuming that they all primarily block lysosomal degradation.

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    Chloroquine is commonly used to study the role of endosomal acidification in cellular processes 2, 3, such as the signaling of intracellular TLRs. Moreover, Chloroquine inhibits autophagy as it raises the lysosomal pH, which leads to inhibition of both fusion of autophagosome with lysosome and lysosomal protein degradation 4. References. 1. Autophagy is an evolutionarily conserved and strictly regulated lysosomal pathway that degrades cytoplasmic material and organelles. Autophagy is activated during stress conditions such as amino acid starvation, unfolded protein response or viral infection. Chloroquine is commonly used to study the role of endosomal acidification in cellular processes 2, 3, such as the signaling of intracellular TLRs. Moreover, Chloroquine inhibits autophagy as it raises the lysosomal pH, which leads to inhibition of both fusion of autophagosome with lysosome and lysosomal protein degradation 4.

     
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