MLIV is typified by accumulation of lipids and membranous materials in intracellular organelles, which was hypothesized to be caused by the altered membrane fusion and fission events. How mutations in TRP-ML1 lead to aberrant lipolysis is not known. Autophagy inhibitors hydroxychloroquine Hair loss plaquenil ELSEVIER Molecular and Biochemical Parasitology 68 1994 209-219 MOLECULAR AND BIOCHEMICAL PARASITOLOGY Enhanced lysosomal acidification leads to increased chloroquine accumulation in CHO cells expressing the pfmdrl gene Helmuth H. G. van Es a,1 Herma Renkema b Hans Aerts b, Erwin Schurr a. 9 a Department of Medicine, McGill University, MontrEal, Canada b The E. C. Slater Institute for. Conversely, viruses that enter the cell via the endocytic pathway require the acidification of these vesicles to trigger the fusogenic activity of their viral fusion proteins 23, 46. Historically, viruses that enter cells by the pH-dependent pathway have been identified by their sensitivity to inhibitors of endosomal/lysosomal acidification. Here we show that lysosomal inhibitors, chloroquine and NH 4 Cl, lead to accumulation of endogenous and ectopically expressed BACE in a variety of cell types, including primary neurons. Furthermore, the inhibition of lysosomal hydrolases results in the redistribution and accumulation of BACE in the late endosomal/lysosomal compartments. Thus, measurement of lysosomal p H revealed that the lysosomes in TRP-ML1 is a lysosomal storage disease typified by the accumulation of lipids and membranous material in intracellular organelles, predominantly lysosomes (reviewed in Refs. Earlier attempts to explain the accumulation of lipids in MLIV focused on hyperactive endocytosis (3). Here we present evidence that MLIV is a metabolic disorder that is not associated with aberrant membrane fusion/fission events. Lysosomal acidification chloroquine Chloroquine analogues in drug discovery new directions of., Inhibition of Endosomal/Lysosomal Degradation Increases. Hydroxychloroquine human antihimeric antibodies Azithromycin and chloroquine additionally inhibited arachidonic acid release and prostaglandin E2 synthesis. Therefore, impairment of lysosomal functions by azithromycin and chloroquine deregulate TLR4 recycling and signaling and phospholipases activation and lead to anti-inflammatory phenotype in LPS-stimulated J774A.1 cells. Impairment of lysosomal functions by azithromycin and.. BACE Is Degraded via the Lysosomal Pathway. Chloroquine C18H26ClN3 - PubChem. Mar 11, 2002 Conversely, viruses that enter the cell via the endocytic pathway require the acidification of these vesicles to trigger the fusogenic activity of their viral fusion proteins 23, 46. Historically, viruses that enter cells by the pH-dependent pathway have been identified by their sensitivity to inhibitors of endosomal/lysosomal acidification. Jan 23, 2017 The increasing evidence suggests that the entry, replication and infection processes of several viruses such as Ebola, Marburg, dengue, Chikungunya, HIV etc. are highly dependent on endosomal‐lysosomal acidification and the activities of several host endosomal proteases ‐ which are also active in acidic pH environments Sun and Tien 2012; Barrow et al. 2013. To investigate the ability of chloroquine, a lysosomotropic autophagy inhibitor, to enhance the anticancer effect of nutrient deprivation. Serum-deprived U251 glioma, B16 melanoma and L929 fibrosarcoma cells were treated with chloroquine in vitro. Cell viability was measured by crystal violet and MTT assay. Oxidative stress, apoptosis/necrosis and intracellular acidification were analyzed by.