Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

Discussion in 'Hydroxychloroquine Sulfate' started by sorgo, 07-Mar-2020.

  1. away New Member

    Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion


    Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that inhibit autophagy by targeting the lysosomes but through distinct mechanisms.

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    Accordingly, PI4K2A depletion or the overexpression its kinase-dead, dominant negative form leads to the buildup of autophagosomes, inhibits autophagic flux and impairs autophagosome-lysosome fusion. RAB7 positive late endosomes/lysosomes are also enriched with PI4P by PI4K2A. Chloroquine inhibits lysozyme activity by increasing pH Mizushima et al. 2010. Bafilomycin-A1 is a V-ATPase inhibitor that can block autophagosome–lysosome fusion and prevent lysosome acidification Yamamoto et al. 1998 ; Klionsky et al. 2008b. We show that CQ mainly inhibits autophagy by impairing autophagosome fusion with lysosomes rather than by affecting the acidity and/or degradative activity of this organelle. Furthermore, CQ induces an autophagy-independent severe disorganization of the Golgi and endo-lysosomal systems, which might contribute to the fusion impairment.

    To address this, we cultured primary rat cortical neurons from E18 embryos and used the Seahorse XF96 analyzer and a targeted metabolomics approach to measure the effects of bafilomycin A1 and chloroquine on bioenergetics and metabolism. Since it is now clear that mitochondrial quality control, particularly in neurons, is dependent on autophagy, it is important to determine whether these compounds modify cellular bioenergetics.

    Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

    Chloroquine for research Cell-culture tested InvivoGen, Inhibition of lysosome degradation on autophagosome.

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  6. Taken together, these findings indicate that BNIP3 depletion abrogates BBM-mediated blockade of autophagic flux and autophagosome-lysosome fusion through recovering the interaction between SNAP29.

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    Autophagic flux defects in cancer. The relationship between autophagy and tumorigenesis has been intensively explored, but whether autophagy plays a role of pro- or anti-tumorigenesis in tumor development and cancer therapy is still controversial 24. Several genetic links have been demonstrated between autophagic defects and cancer, implying that autophagy is a part of tumor suppressor pathways 25. Chloroquine is a lysosomotropic weak base, which in the monoprotonated form diffuses into the lysosome, where it becomes diprotonated and becomes trapped. Protonated chloroquine then changes the lysosomal pH, thereby inhibiting autophagic degradation in the lysosomes. We show that CQ mainly inhibits autophagy by impairing autophagosome fusion with lysosomes rather than by affecting the acidity and/or degradative activity of this organelle. Furthermore, CQ.

     
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  8. Armee Guest

    This is not a list of all drugs or health problems that interact with chloroquine. Chloroquine - FDA prescribing information, side effects and uses Chloroquine and hydroxychloroquine for cancer therapy Autophagy inhibitor chloroquine increases sensitivity to.
     
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  10. Natalija Guest

    Changes in glycosylated hemoglobin after initiation of. In addition, hydroxychloroquine HCQ, an FDA‐approved DMARD for the treatment of RA and lupus, has been shown in at least 2 randomized controlled trials to improve diabetes control in patients without rheumatic disease 21, 22. One large epidemiologic study also showed that HCQ reduces the risk of DM among patients with RA.

    Hydroxychloroquine and Risk of Diabetes in Patients With.