6- mercaptopurine (6-mp) is widely used in clinic as an immunosuppressive for treatment of acute lymphocytic leukemia, crohn's disease, and ulcerative colitis with documented unpredictable hepatotoxicity. the potential molecular cytotoxic mechanisms of 6-mp against isolated rat hepatocytes were searched in this study using “accelerated cytotoxicity mechanism screening (acms)” techniques. t...

dacarbazine is an antitumor prodrug which is used for the treatment of malignant metastatic melanoma and hodgkin’s disease. it requires initial activation in liver through an n-demethylationreaction. the active metabolite prevents the progress of disease via alkylation of guanine bases in dna strands. in order to investigate the importance of imidazole ring and its dynamictautomerization in ant...

Lysosomes are dynamic structures capable of fusing with endosomes as well as other lysosomes. We examined the biochemical requirements for homotypic lysosome fusion in vitro using lysosomes obtained from rabbit alveolar macrophages or the cultured macrophage-like cell line, J774E. The in vitro assay measures the formation of a biotinylated HRP-avidin conjugate, in which biotinylated HRP and avi...

Abstract IL-1β is an inflammatory cytokine mainly secreted by myeloid cells in response to infection or sterile tissue damage. Non-canonical secretion of from macrophages downstream activated NLRP3/caspase-1 inflammasomes the best-characterized model; this mediated caspase-1 cleavage GSDMD allowing N-GSDMD form pores plasma membrane that act as conduits for release and inducers pyroptosis a lyt...

Dysferlin has recently been reported to participate in cell membrane repair in muscle and other cells through lysosome fusion. Given that lysosome fusion is a crucial mechanism that leads to membrane raft clustering, the present study attempted to determine whether dysferlin is involved in this process and its related signalling, and explores the mechanism underlying dysferlin-mediated lysosome...

The endoplasmic reticulum (ER) comprises morphologically and functionally distinct domains, sheets interconnected tubules. These domains undergo dynamic reshaping, in response to changes the cellular environment. However, mechanisms behind this rapid remodeling within minutes are largely unknown. Here, we report that ER is actively driven by lysosomes, following lysosome repositioning nutrition...

Whereas the mechanisms involved in autophagosome formation have been extensively studied for the past 2 decades, those responsible for autophagosome-lysosome fusion have only recently begun to garner attention. In this study, we report that the multisubunit BORC complex, previously implicated in kinesin-dependent movement of lysosomes toward the cell periphery, is required for efficient autopha...

introduction: l.pneumophila has been known as a facultative intracellular bacterium which could proliferate within mammalian macrophages and a wide spectrum of free-living protozoa such as a. castellianii. its pathgenicity for both host cell types could be mostly dependent on the intracellular living conditions. materials and methods: l. pneumophila-infected acanthamoeba were examined by a flou...