Overexpression of CHMP6 Induces Cellular Oncosis and Apoptosis in HeLa Cells

Fu, Dongxu; Tian, Linjie; Peng, Zhi; Deng, Wei‐Wei; Ma, Dalong; Shi, Taiping; Li, Dianjun; Wang, Ying

doi:10.1271/bbb.80458

Cited by 8 publications

(9 citation statements)

References 29 publications

(32 reference statements)

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“…In the presence of resistant CHMP3 cDNA, siCHMP3 increased relative L1 activity to 69% from 61%. Overexpression of CHMP6 is known to cause cytotoxicity [67], which is consistent with the low levels of G418 colony formation when CHMP6 is overexpressed (Fig 3D, resistant CHMP6 cDNA + scramble siRNA). This makes the results of the CHMP6 rescue ambiguous as compared to the rescue with ALIX and CHMP3 (Fig 3D).…”

Section: Resultssupporting

confidence: 77%

A conserved role for the ESCRT membrane budding complex in LINE retrotransposition

et al. 2017

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Long interspersed nuclear element-1s (LINE-1s, or L1s) are an active family of retrotransposable elements that continue to mutate mammalian genomes. Despite the large contribution of L1 to mammalian genome evolution, we do not know where active L1 particles (particles in the process of retrotransposition) are located in the cell, or how they move towards the nucleus, the site of L1 reverse transcription. Using a yeast model of LINE retrotransposition, we identified ESCRT (endosomal sorting complex required for transport) as a critical complex for LINE retrotransposition, and verified that this interaction is conserved for human L1. ESCRT interacts with L1 via a late domain motif, and this interaction facilitates L1 replication. Loss of the L1/ESCRT interaction does not impair RNP formation or enzymatic activity, but leads to loss of retrotransposition and reduced L1 endonuclease activity in the nucleus. This study highlights the importance of the ESCRT complex in the L1 life cycle and suggests an unusual mode for L1 RNP trafficking.

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Section: Resultssupporting

confidence: 77%

A conserved role for the ESCRT membrane budding complex in LINE retrotransposition

et al. 2017

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“…Furthermore, the examination of the morphological changes of fluopsin C-treated MCF-7 and MD-MBA-231 cells via time-lapse microscopy revealed cellular features characteristic of oncotic death, such as extensive cytoplasmic vacuolization, cellular and organelle swelling, and rupture of the plasma membrane, typical features of oncosis [4,5] .…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, oncosis is a process of passive cell death related to energy depletion, leading to the impairment of cell membrane ionic pumps, the swelling of the cell, the formation of cell surface blebs, the condensation of mitochondria, and an increase in membrane permeability. Oncosis is the pattern of change in infarcts and zonal killing following chemical toxicity [4,5] .…”

Section: Introductionmentioning

confidence: 99%

Fluopsin C induces oncosis of human breast adenocarcinoma cells

Jiang

Cui

et al. 2013

Acta Pharmacol Sin

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Aim: Fluopsin C, an antibiotic isolated from Pseudomonas jinanesis, has shown antitumor effects on several cancer cell lines. In the current study, the oncotic cell death induced by fluopsin C was investigated in human breast adenocarcinoma cells in vitro. Methods: Human breast adenocarcinoma cell lines MCF-7 and MD-MBA-231 were used. The cytotoxicity was evaluated using MTT assay. Time-lapse microscopy and transmission electron microscopy were used to observe the morphological changes. Cell membrane integrity was assessed with propidium iodide (PI) uptake and lactate dehydrogenase (LDH) assay. Flow cytometry was used to measure reactive oxygen species (ROS) level and mitochondrial membrane potential (Δψm). A multimode microplate reader was used to analyze the intracellular ATP level. The changes in cytoskeletal system were investigated with Western blotting and immunostaining.Results: Fluopsin C (0.5-8 μmol/L) reduced the cell viability in dose-and time-dependent manners. Its IC 50 values in MCF-7 and MD-MBA-231 cells at 24 h were 0.9 and 1.03 μmol/L, respectively. Fluopsin C (2 μmol/L) induced oncosis in both the breast adenocarcinoma cells characterized by membrane blebbing and swelling, which was blocked by pretreatment with the pan-caspase inhibitor Z-VAD-fmk. In MCF-7 cells, fluopsin C caused PI uptake into the cells, significantly increased LDH release, induced cytoskeletal system degradation and ROS accumulation, decreased the intracellular ATP level and Δψm. Noticeably, fluopsin C exerted comparable cytotoxicity against the normal human hepatocytes (HL7702) and human mammary epithelial cells with the IC 50 values at 24 h of 2.7 and 2.4 μmol/L, respectively. Conclusion: Oncotic cell death was involved in the anticancer effects of fluopsin C on human breast adenocarcinoma cells in vitro. The hepatoxicity of fluopsin C should not be ignored.

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“…Mitochondrial membrane potential (Δψm) was determined by flow cytometry using 3,3′-dihexyloxacarbocyanine iodide (DiOC6(3)) (DiOC6(3) Detection Kit; Life Technologies), using DiOC6(3) concentrations specific for mitochondria as described [27]. …”

Section: Methodsmentioning

confidence: 99%

Mechanisms of modified LDL-induced pericyte loss and retinal injury in diabetic retinopathy

et al. 2012

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Aims/hypothesis In previous studies we have shown that extravasated, modified LDL is associated with pericyte loss, an early feature of diabetic retinopathy (DR). Here we sought to determine detailed mechanisms of this LDL-induced pericyte loss. Methods Human retinal capillary pericytes (HRCP) were exposed to ‘highly-oxidised glycated’ LDL (HOG-LDL) (a model of extravasated and modified LDL) and to 4-hydroxynonenal or 7-ketocholesterol (components of oxidised LDL), or to native LDL for 1 to 24 h with or without 1 h of pretreatment with inhibitors of the following: (1) the scavenger receptor (polyinosinic acid); (2) oxidative stress (N-acetyl cysteine); (3) endoplasmic reticulum (ER) stress (4-phenyl butyric acid); and (4) mitochondrial dysfunction (cyclosporin A). Oxidative stress, ER stress, mitochondrial dysfunction, apoptosis and autophagy were assessed using techniques including western blotting, immunofluorescence, RT-PCR, flow cytometry and TUNEL assay. To assess the relevance of the results in vivo, immunohistochemistry was used to detect the ER stress chaperon, 78 kDa glucose-regulated protein, and the ER sensor, activating transcription factor 6, in retinas from a mouse model of DR that mimics exposure of the retina to elevated glucose and elevated LDL levels, and in retinas from human participants with and without diabetes and DR. Results Compared with native LDL, HOG-LDL activated oxidative and ER stress in HRCP, resulting in mitochondrial dysfunction, apoptosis and autophagy. In a mouse model of diabetes and hyperlipidaemia (vs mouse models of either condition alone), retinal ER stress was enhanced. ER stress was also enhanced in diabetic human retina and correlated with the severity of DR. Conclusions/interpretation Cell culture, animal, and human data suggest that oxidative stress and ER stress are induced by modified LDL, and are implicated in pericyte loss in DR.

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Overexpression of CHMP6 Induces Cellular Oncosis and Apoptosis in HeLa Cells

Cited by 8 publications

References 29 publications

A conserved role for the ESCRT membrane budding complex in LINE retrotransposition

A conserved role for the ESCRT membrane budding complex in LINE retrotransposition

Fluopsin C induces oncosis of human breast adenocarcinoma cells

Mechanisms of modified LDL-induced pericyte loss and retinal injury in diabetic retinopathy

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