Chloroquine lysosomal degradation

Discussion in 'Canadian Drugs' started by romand, 24-Feb-2020.

  1. RUS-HOSTING.RU Well-Known Member

    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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    Third, downregulation of CTLA-4 by Ipilimumab is prevented by an inhibitor of lysosomal degradation but not by proteasome inhibitor, affirming the role of antibody in inducing lysosomal degradation. I am trying to block lysosomal degradation in tubular epithelial cells derived from mice kidneys. To that end, I am treating these cells with 100 micromolar Chloroquine 16hours. chloroquine. 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.

    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

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  6. Chloroquine is also a lysosomotropic agent, meaning it accumulates preferentially in the lysosomes of cells in the body. The pK a for the quinoline nitrogen of chloroquine is 8.5, meaning it is about 10% deprotonated at physiological pH as calculated by the Henderson-Hasselbalch equation. This decreases to about 0.2% at a lysosomal pH of 4.6.

    • Chloroquine - Wikipedia.
    • Chloroquine for research Cell-culture tested InvivoGen.
    • Lysosomal Degradation of Junctional Proteins IntechOpen.

    Chloroquine and methylamine, which accumulate in lysosomes by virtue of their weak base properties, inhibited hepatocytic protein degradation to the same extent as ammonia, with no additivity. These compounds therefore seem to block the lysosomal pathway of protein degradation selectively and completely. Chloroquine also increased expression of LC3B-II and ATG5 mRNA Figure 5B and 5C. To determine the impact of chloroquine on protein degradation and lysosome function, we examined the effects of chloroquine on p62, a protein known to be uniquely degraded by autophagy pathways. This accumulation leads to inhibition of lysosomal enzymes that require an acidic pH, and prevents fusion of endosomes and lysosomes. 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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