期刊
CELL CYCLE
卷 12, 期 16, 页码 2636-2642出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.25650
关键词
antimycin A; menadione; mitochondrial membrane permeabilization; rotenone; U2OS cells; Z-VAD-fmk
类别
资金
- Ligue contre le Cancer (equipe labelisee)
- Agence National de la Recherche
- AXA Chair for Longevity Research
- Association pour la Recherche sur le Cancer
- Canceropole Ile-de-France
- Institut National du Cancer (INCa)
- Fondation Bettencourt-Schueller
- Fondation de France
- Fondation pour la Recherche Medicale
- European Commission (ArtForce)
- European Research Council
- LabEx Immuno-Oncology
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (Socrate)
- Cancer Research and Personalized Medicine (Carpem)
- Paris Alliance of Cancer Research Institutes (PACRI)
- Air Liquide
Although chemically non-reactive, inert noble gases may influence multiple physiological and pathological processes via hitherto uncharacterized physical effects. Here we report a cell-based detection system for assessing the effects of pre-defined gas mixtures on the induction of apoptotic cell death. In this setting, the conventional atmosphere for cell culture was substituted with gas combinations, including the same amount of oxygen (20%) and carbon dioxide (5%) but 75% helium, neon, argon, krypton, or xenon instead of nitrogen. The replacement of nitrogen with noble gases per se had no effects on the viability of cultured human osteosarcoma cells in vitro. Conversely, argon and xenon (but not helium, neon, and krypton) significantly limited cell loss induced by the broad-spectrum tyrosine kinase inhibitor staurosporine, the DNA-damaging agent mitoxantrone and several mitochondrial toxins. Such cytoprotective effects were coupled to the maintenance of mitochondrial integrity, as demonstrated by means of a mitochondrial transmembrane potential-sensitive dye and by assessing the release of cytochrome c into the cytosol. In line with this notion, argon and xenon inhibited the apoptotic activation of caspase-3, as determined by immunofluorescence microscopy coupled to automated image analysis. The antiapoptotic activity of argon and xenon may explain their clinically relevant cytoprotective effects.
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