Chloroquine and p62

Discussion in 'Canadian Pharmaceuticals Online' started by Avert, 28-Feb-2020.

  1. baraban User

    Chloroquine and p62


    Chloroquine has been extensively used in mass drug administrations, which may have contributed to the emergence and spread of resistance. It is recommended to check if chloroquine is still effective in the region prior to using it.

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    There is a growing evidence that antimalarial chloroquine could be re-purposed for cancer treatment. A dozen of clinical trials have been initiated within the past 10 years to test the potential of chloroquine as an adjuvant treatment for therapy–refractory cancers including glioblastoma, one of the most aggressive human cancers. While there is considerable evidence for the efficacy and. With anti-Keap1 or anti-Lc3 or anti-p62 antibodies. c 6-OhDA induces Keap1-p62 interaction. hA-Keap1 transfected heK293T cells were treated with 6-OhDA for 6 hours. cells were then lysed and followed with hA immunoprecipitation. The endogenous p62 pulled down by Keap1 was detected by western blotting. In addition to genetic means, autophagy can be disabled by the lysosomal inhibitor chloroquine or by bortezomib, which blocks autophagy via a cathepsin-dependent mechanism resulting in up-regulation of p62. p62 is rich in protein-interacting sequences and contains domains that include a protein-protein interaction module PB1 that facilitates its oligomerization, a ubiquitin-associated UBA 3 domain, and an LC3 interaction region that are essential for p62 function 8, 13, 14.

    The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations. In areas where resistance is present, other antimalarials, such as mefloquine or atovaquone, may be used instead.

    Chloroquine and p62

    Anti-SQSTM1 / p62 antibody ab155686 Abcam, Keap1 facilitates p62-mediated ubiquitin aggregate clearance.

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  5. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy.

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    Antimalarial drug chloroquine inhibits autophagy of glioma cells and has been tested as an antineoplastic agent in a small clinical study 25. 10 nM Baf A1 for 2 hours, lysed, and analyzed by immunoblot for p62, an LC3-binding protein and marker of autophagic flux. Degradation of p62 indicates induction of autophagy. b-Tubulin shown as a. In agreement, blocking lysosomal degradation using chloroquine CQ rescued LC3-II and p62 breakdown. Interestingly, caspase inhibition by ZVAD-fmk also increased the level of LC3-II and p62, suggesting that caspase signaling may modulate the autophagic process Figure 4D. Dec 13, 2016 The interactions of p62 and the UPS, autophagy and ubiquitinated proteins. Upon UPS inhibition, p62 is upregulated and phosphorylated on S405 and S409, which can facilitate the degradation of ubiquitinated cargoes via autophagy. p62 synthesis is induced by an increase in Nrf2 following UPS deficiency.

     
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