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- Title
Cold atmospheric nitrogen plasma induces metal‐initiated cell death by cell membrane rupture and mitochondrial perturbation.
- Authors
Iuchi, Katsuya; Fukasawa, Mami; Murakami, Tomoyuki; Hisatomi, Hisashi
- Abstract
Cold atmospheric plasma (CAP) is a novel biomedical tool used for cancer therapy. A device using nitrogen gas (N2CAP) produced CAP that induced cell death through the production of reactive nitrogen species and an increase in intracellular calcium. In this study, we investigated the effect of N2CAP‐irradiation on cell membrane and mitochondrial function in human embryonic kidney cell line 293T. We investigated whether iron is involved in N2CAP‐induced cell death, as deferoxamine methanesulfonate (an iron chelator) inhibits this process. We found that N2CAP induced cell membrane disturbance and loss of mitochondrial membrane potential in an irradiation time‐dependent manner. BAPTA‐AM, a cell‐permeable calcium chelator, inhibited N2CAP‐induced loss of mitochondrial membrane potential. These results suggest that disruption of intracellular metal homeostasis was involved in N2CAP‐induced cell membrane rupture and mitochondrial dysfunction. Moreover, N2CAP irradiation generated a time‐dependent production of peroxynitrite. However, lipid‐derived radicals are unrelated to N2CAP‐induced cell death. Generally, N2CAP‐induced cell death is driven by the complex interaction between metal movement and reactive oxygen and nitrogen species produced by N2CAP. Significance statement: CAPs exhibit various biological activities via complicated pathways, and can effectively induce cell death in cancer cell lines. To understand the mechanism of CAP‐induced cell death, we investigated whether N2CAP affects the cellular function in a cultured cell line. Here, we show that N2CAP induced mitochondrial dysfunction and plasma membrane disruption in 293T cells. Moreover, we demonstrate that intracellular calcium and iron are involved in CAP‐induced cellular dysfunction. Thus, the orchestration of intracellular metal movement is essential for N2CAP‐induced cell death.
- Subjects
INTRACELLULAR calcium; CELL death; NITROGEN plasmas; ATMOSPHERIC nitrogen; CELL membranes; MITOCHONDRIAL membranes; CELL physiology
- Publication
Cell Biochemistry & Function, 2023, Vol 41, Issue 6, p687
- ISSN
0263-6484
- Publication type
Article
- DOI
10.1002/cbf.3823