In MDA-MB-231 cells, immunolocalization and brefeldin A protein transport blocking studies revealed that there was a propensity for newly synthesized Cx43 to be transported to lysosomes. On the other hand, light and electron microscopic analysis of BICR-M1R cells showed that Cx43 gap junctions were prevalent with a subpopulation of intracellular Cx43 localized to lysosomes. Why does plaquenil make my stomach bleed Plaquenil icd 9 Does plaquenil stop progression of lupus Intracellular connexins also colocalized with p62, a protein that might serve as a cargo receptor for autophagic degradation. Starvation induced a decrease in connexin levels that was blocked by treatment with chloroquine, a lysosomal protease inhibitor, or by knockdown of the autophagy-related protein Atg5. Lysosomal protease-independent degradation of PUMA protein. Chloroquine is generally considered to exert its drug effect through inhibition of lysosomal acidification. Because melanoma cells treated with CQ increased the levels of PUMA protein, we explored whether a lysosomal process causes PUMA protein destabilization. In biomedicinal science, chloroquine is used for in vitro experiments to inhibit lysosomal degradation of protein products. References edit ^ a b c d e f g h i j k l "Aralen Phosphate". Interestingly, lactacystin inhibition of proteosomal degradation in MDA-MB-231 cells resulted in a marked increase in phosphorylated Cx43 at the expense of non-phosphorylated Cx43, and this change corresponded with an increase in “oversized” gap junction plaques. In both cell types, Western blots revealed a notable increase in total cellular Cx43 in response to lysosome inhibitors. Chloroquine protein degradation Questions with answers in CHLOROQUINE Science topic, Chloroquine Promotes Apoptosis in Melanoma Cells by. Chloroquine and doxycycline similar drugs Chloroquine's potential chemosensitizing and radiosensitizing activities in cancer may be related to its inhibition of autophagy, a cellular mechanism involving lysosomal degradation that minimizes the production of reactive oxygen species ROS related to tumor reoxygenation and tumor exposure to chemotherapeutic agents and radiation. Chloroquine C18H26ClN3 - PubChem. Chloroquine - Wikipedia. Lysosomal and Proteasomal Degradation Play Distinct Roles.. Chloroquine and methylamine, which accumulate in lysosomes by virtue of their weak base properties, inhibited hepatocytic protein degradation to the same extent as ammonia, with no additivity. These compounds therefore seem to block the lysosomal pathway of protein degradation selectively and completely. However, the incidence of gap junction plaques did increase by 61–88% when lysosomal and proteasomal degradation were simultaneously inhibited Fig. 6, D, F, and H, double arrows, and I, suggesting that it was proteasomal, but not lysosomal, inhibition that was responsible for the increase in number of gap junction plaques in MDA-MB-231vCx43. Thus, the low levels of ubiquitinated proteins detected upon chloroquine treatment were not caused by a lack of reactivity of the antibody with Lys 63-ubiquitinated proteins. We considered if the limited accumulation of ubiquitinated proteins observed under chloroquine treatment could be due to proteasomal inhibition, so we compared the effect of chloroquine and epoxomicin on proteasome activity.