Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

Discussion in 'Hydroxychloroquine Sulfate 200 Mg' started by andrey3, 08-Mar-2020.

  1. Dennizan 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.

    Hydroxychloroquine risk Hydroxychloroquine effects on kidneys

    Usually I use bafilomycin A a specific inhibitor of vacuolar-type H+-ATPase, or chloroquine CQ lysosomotropic agent that inhibit lysosomal acidification, and less expensive both are reported. As described above, if cells are treated with lysosomotropic reagents such as ammonium chloride, chloroquine, or bafilomycin A 1, which inhibit acidification inside the lysosome or inhibit autophagosome-lysosome fusion, or with inhibitors of lysosomal proteases such as E64d and pepstatin A, the degradation of LC3-II is blocked, resulting in the. Recent in vitro and in vivo studies revealed that chloroquine affects the endo-lysosomal system and golgi complex thereby modulates autophagic flux through decreasing autophagosome-lysosome fusion. This study invalidated lysosomal degradation function of chloroquine.

    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

    Inhibition of lysosome degradation on autophagosome., Methods in Mammalian Autophagy Research - PubMed Central PMC

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  3. Jan 23, 2019 In the present study, we provide direct evidence that FoxO1 inhibits autophagosome-lysosome fusion leading to ECs autophagic apoptosis in diabetes. We found inadequate autophagy with impaired autophagosome-lysosomal fusion in ECs from diabetic patients.

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    Nov 15, 2019 Here we report that exposure to BPA inhibits ATG5-dependent autophagy by impairing autophagosome-lysosome fusion. Furthermore, BPA blocks Stx17-Snap29-Vamp8 complex formation. The autophagosome-lysosome fusion defects caused by BPA also increase intracellular ROS level and causes lipid droplet accumulation. Chloroquine CQ, a 4-aminoquinoline compound, has long been prescribed for the treatment of malaria- 1, autoim mune disorders2 and viral infections 3. It functions primarily by inhibiting lysosomal proteases and blocking autophagosome-lysosome fusion 4. In the range of neutral pH, CQ can freely diffuse across the plasma membrane but Chemotherapy failure is a major cause of recurrence and poor prognosis in colorectal cancer CRC patients. Inhibition of autophagy is a promising str

     
  4. Nee Well-Known Member

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