Atmospheric pressure room temperature plasma jets facilitate oxidative and nitrative stress and lead to endoplasmic reticulum stress dependent apoptosis in HepG2 cells

• Published in: PloS one Vol. 8; no. 8; p. e73665
• Main Authors: Zhao, Shasha, Xiong, Zilan, Mao, Xiang, Meng, Dandan, Lei, Qian, Li, Yin, Deng, Pengyi, Chen, Mingjie, Tu, Min, Lu, Xinpei, Yang, Guangxiao, He, Guangyuan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.08.2013; Public Library of Science (PLoS)
• Subjects: Acetylcysteine; Antioxidants; Antioxidants - metabolism; Apoptosis; Atmospheric Pressure; Biophysics; Calcium; Calcium (intracellular); Calcium homeostasis; Carbonyls; Caspase 12 - metabolism; Catalase; Catalase - metabolism; Cell growth; Content analysis; Deactivation; Education; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Enzyme Precursors - metabolism; Enzymes; Free radicals; Genetic engineering; Glutathione; Glutathione - metabolism; Heat-Shock Proteins - metabolism; Hep G2 Cells; Homeostasis; Humans; Inactivation; Injury analysis; International cooperation; Laboratories; Life sciences; Nitrogen; Nitrotyrosine; Oxidation; Oxidative Stress; Oxygen; Plasma jets; Proteins; Reactive nitrogen species; Reactive Nitrogen Species - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rodents; Room temperature; Skin cancer; Stress; Stresses; Superoxide dismutase; Superoxide Dismutase - metabolism; Temperature; Toxicity; Transcription Factor CHOP - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073665

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.