Methuosis Contributes to Jaspine-B-Induced Cell Death
| Autor: | Núria Bielsa, Mireia Casasampere, Jose Luis Abad, Carlos Enrich, Antonio Delgado, Gemma Fabriàs, Jose M. Lizcano, Josefina Casas |
|---|---|
| Přispěvatelé: | Ministerio de Ciencia e Innovación (España) |
| Rok vydání: | 2022 |
| Předmět: |
Cell Survival
Apoptosis Endosomes Mechanistic Target of Rapamycin Complex 1 Catalysis Sphingosine/analogs & derivatives Inorganic Chemistry Phosphatidylinositol 3-Kinases Mice SDG 3 - Good Health and Well-being Sphingosine Neoplasms Cell Line Tumor Sphingolipids/pharmacology Autophagy Animals Physical and Theoretical Chemistry Molecular Biology Spectroscopy Sphingolipids Cytoplasmic vacuolization Methuosis Cell Death Organic Chemistry General Medicine Fibroblasts autophagy methuosis apoptosis sphingolipids cytoplasmic vacuolization Computer Science Applications |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname International Journal of Molecular Sciences; Volume 23; Issue 13; Pages: 7257 |
| Popis: | Methuosis is a type of programmed cell death in which the cytoplasm is occupied by fluid-filled vacuoles that originate from macropinosomes (cytoplasmic vacuolation). A few molecules have been reported to behave as methuosis inducers in cancer cell lines. Jaspine B (JB) is a natural anhydrous sphingolipid (SL) derivative reported to induce cytoplasmic vacuolation and cytotoxicity in several cancer cell lines. Here, we have investigated the mechanism and signalling pathways involved in the cytotoxicity induced by the natural sphingolipid Jaspine B (JB) in lung adenocarcinoma A549 cells, which harbor the G12S K-Ras mutant. The effect of JB on inducing cytoplasmic vacuolation and modifying cell viability was determined in A549 cells, as well as in mouse embryonic fibroblasts (MEF) lacking either the autophagy-related gene ATG5 or BAX/BAK genes. Apoptosis was analyzed by flow cytometry after annexin V/propidium iodide staining, in the presence and absence of z-VAD. Autophagy was monitored by LC3-II/GFP-LC3-II analysis, and autophagic flux experiments using protease inhibitors. Phase contrast, confocal, and transmission electron microscopy were used to monitor cytoplasmic vacuolation and the uptake of Lucifer yellow to assess macropinocyosis. We present evidence that cytoplasmic vacuolation and methuosis are involved in Jaspine B cytotoxicity over A549 cells and that activation of 5' AMP-activated protein kinase (AMPK) could be involved in Jaspine-B-induced vacuolation, independently of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 1 (PI3K/Akt/mTORC1) axis. This research was funded by MCIN/AEI/10.13039/501100011033 and by the European Union (“ERDF A way of making Europe”), grants number CTQ2017-85378-R and PID2020-113813RB-I00 (to G.F.) and PID2019-107561RB-I00 (to J.M.L.). |
| Databáze: | OpenAIRE |
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