Chloroquine bafilomycin a1 conventional autophagy

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  1. jeniaanddia New Member

    Chloroquine bafilomycin a1 conventional autophagy

    The end result is an accumulation of mature but undigested autophagosomes (). This drug binds tightly though noncovalently to the V-ATPase, although the identification of the target subunit has been controversial, with different groups reporting the 100- to 115-k D a subunit and the 14- to 17-k Da proteolipid c subunit as the binding sites ().

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    The bafilomycins are a family of macrolide antibiotics produced from a variety of Streptomycetes. Their chemical structure is defined by a 16-membered lactone ring scaffold. Bafilomycins exhibit a wide range of biological activity, including anti-tumor, anti-parasitic, immunosuppressant and anti-fungal activity. The most used bafilomycin is bafilomycin A1, a potent inhibitor of cellular autophagy. Bafilomycins have also been found to act as ionophores, transporting potassium K+ across biological The core autophagy-related Atg complexes in mammals are ULK1 protein kinases, Atg9-WIPI1 and Vps34-Beclin1 class III PI3-kinase complexes, and the Atg12 and LC3 conjugation systems. PI 3-binding proteins, PI3-phosphatases and Rab proteins also contribute significantly to autophagy. Bafilomycin A1 BafA1, a macrolide antibiotic, is a known inhibitor of the latter stages of autophagy, inhibiting fusion between autophagosomes and lysosomes by inhibiting vacuolar H + ATPase 10. This has been demonstrated to result in a marked accumulation of autophagosomes, concomitant with apoptotic cell death 11, 12.

    More promising are some recently described members of another structural class of compounds, the benzolactone enamides, which have recently been shown to potently inhibit mammalian V-ATPase with high selectivity (). However, these drugs are of limited use for p H perturbation studies, as they require somewhat higher concentrations than the macrolide antibiotics and are not as selective as other V-ATPase inhibitors ().

    Chloroquine bafilomycin a1 conventional autophagy

    Inhibition of autophagy with bafilomycin and chloroquine., FAQs - Autophagy and LC3 - Novus Biologicals

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  4. Nov 08, 2011 We first tested the effects of bafilomycin A1, a conventional inhibitor of autophagic maturation, which acts as an antagonist of vacuolar H + ATPase and prevents lumenal acidification and autophagosomal cargo degradation. If induction of autophagy acted to degrade IL‐1β, then bafilomycin A1 was expected to increase IL‐1β levels.

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    When added separately, chloroquine or high concentrations of bafilomycin A1 ≥10 nM induced a dose-dependent inhibition of autophagy as measured by an increase in LC3-II, a marker specific for autophagosomes, followed by caspase-3 activation and cell death. AUTOPHAGY, BAFILOMYCIN AND CELL DEATH Figure 1. Bid deficiency does not prevent chloroquine-induced death of CGNs. Cultured CGNs were prepared from Bid-deficient vs. wild-type brains and cultured as previously described.16After four days in vitro, CGNs were treated with chloroquine 20 µM for 24 h then measured for viability using To investigate the link between autophagy and degradation of ubiquitinated proteins, SK-N-SH cells were treated with three different autophagy inhibitors, namely chloroquine CQ, 100 μ m, ammonium chloride NH 4 Cl, 10 m m, and bafilomycin A1 200 n m at concentrations reported in the literature to inhibit autophagy. We compared the effects.

  5. MC Moderator

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  6. kelser Moderator

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  7. Emane New Member

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