title: Atmospheric pressure room temperature plasma jets facilitate oxidative and nitrative stress and lead to endoplasmic reticulum stress dependent apoptosis in HepG2 cells.
abstract: Atmospheric pressure room temperature plasma jets (APRTP-Js) that can emit a mixture of different active species have recently found entry in various medical applications. Apoptosis is a key event in APRTP-Js-induced cellular toxicity, but the exact biological mechanisms underlying remain elusive. Here, we explored the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in APRTP-Js-induced apoptosis using in vitro model of HepG2 cells. We found that APRTP-Js facilitated the accumulation of ROS and RNS in cells, which resulted in the compromised cellular antioxidant defense system, as evidenced by the inactivation of cellular antioxidants including glutathione (GSH), superoxide dismutase (SOD) and catalase. Nitrotyrosine and protein carbonyl content analysis indicated that APRTP-Js treatment caused nitrative and oxidative injury of cells. Meanwhile, intracellular calcium homeostasis was disturbed along with the alteration in the expressions of GRP78, CHOP and pro-caspase12. These effects accumulated and eventually culminated into the cellular dysfunction and endoplasmic reticulum stress (ER stress)-mediated apoptosis. The apoptosis could be markedly attenuated by N-acetylcysteine (NAC, a free radical scavenger), which confirmed the involvement of oxidative and nitrative stress in the process leading to HepG2 cell apoptosis by APRTP-Js treatment.
authors.affiliation: The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, The Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science & Technology (HUST), Wuhan, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhao
authors.forename: Zilan
authors.initials: Z
authors.lastname: Xiong
authors.forename: Xiang
authors.initials: X
authors.lastname: Mao
authors.forename: Dandan
authors.initials: D
authors.lastname: Meng
authors.forename: Qian
authors.initials: Q
authors.lastname: Lei
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.forename: Pengyi
authors.initials: P
authors.lastname: Deng
authors.forename: Mingjie
authors.initials: M
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Tu
authors.forename: Xinpei
authors.initials: X
authors.lastname: Lu
authors.forename: Guangxiao
authors.initials: G
authors.lastname: Yang
authors.forename: Guangyuan
authors.initials: G
authors.lastname: He
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001274:Atmospheric Pressure; D053454:Caspase 12 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D004792:Enzyme Precursors / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D000975:Antioxidants; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D004792:Enzyme Precursors; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; D002374:Catalase; D013482:Superoxide Dismutase; D053454:Caspase 12; D005978:Glutathione