title: Plasma-activated medium-induced intracellular zinc liberation causes death of SH-SY5Y cells.
abstract: Plasma is an ionized gas consisting of ions, electrons, free radicals, neutral particles, and photons. Plasma-activated medium (PAM), which is prepared by the irradiation of cell-free medium with non-thermal atmospheric pressure plasma, induces cell death in various types of cancer cell. Since PAM contains reactive oxygen species (ROS), its anti-cancer effects are thought to be attributable to oxidative stress. Meanwhile, oxidative stress has been shown to induce the liberation of zinc (Zn(2+)) from intracellular Zn(2+) stores and to provoke Zn(2+)-dependent cell death. In this study, we thus examined whether Zn(2+) is involved in PAM-induced cell death using human neuroblastoma SH-SY5Y cells. Exposure to PAM triggered cell death in SH-SY5Y cells. The cell-permeable Zn(2+) chelator N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) protected against PAM-induced cell death. Zn(2+) imaging using the fluorescent Zn(2+) probe FluoZin-3 revealed that PAM elicited a rise of intracellular free Zn(2+). In addition, PAM stimulated PARP-1 activation, mitochondrial ROS generation, and the depletion of intracellular NAD(+) and ATP. These findings suggest that PAM-induced PARP-1 activation causes energy supply exhaustion. Moreover, TPEN suppressed all of these events elicited by PAM. Taken together, we demonstrated here that Zn(2+) released from intracellular Zn(2+) stores serves as a key mediator of PAM-induced cell death in SH-SY5Y cells.
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: harah@gifu-pu.ac.jp.
authors: Hirokazu
authors: H
authors: Hara
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Miko
authors: M
authors: Taniguchi
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Mari
authors: M
authors: Kobayashi
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Tetsuro
authors: T
authors: Kamiya
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors: Tetsuo
authors: T
authors: Adachi
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005021:Ethylamines / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D058626:Plasma Gases / Q000737:chemistry*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D003470:Culture Media; D005021:Ethylamines; C511824:N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine; D058626:Plasma Gases; D011725:Pyridines; D017382:Reactive Oxygen Species; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D015032:Zinc
keywords: Cell death; Non-thermal atmospheric pressure plasma; PARP-1; Reactive oxygen species; Zinc; Zinc-binding protein