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.

Induction of Apoptosis by Hypertension Via Endoplasmic Reticulum Stress

“…To address the enhanced synthesis of secretory proteins when the ER is overloaded, molecular compensatory mechanisms 1) upregulate ER chaperones; 2) reduce translation, decreasing the load of new protein synthesis, and 3) degrade misfolded proteins within the ER [10]. When ER stress conditions persist, the initiation of apoptotic processes is promoted by the transcriptional induction of C/EBP homologous protein (CHOP/GADD153) [11], the caspase-12-dependent pathway [12], and activation of the c-Jun NH2-terminal kinase (JNK)-dependent pathway [13]. …”

“…One major pathway of the UPR increases the expression of ER-localised molecular chaperones, such as GRP78, which can contribute to repairing unfolded proteins. The induction of GRP78 has been widely used as a marker for ER stress and initiation of the UPR [12]. Furthermore, GRP78 serves as a master modulator for the UPR network by binding to the ER stress sensors, including PKR-like ER kinase (PERK), inositol requiring 1 (IRE1), and transcription factor 6 (ATF6), inhibiting their activation [15].…”

Plasma Medicine: A Brief Introduction

“…Investigators reported that the effects of LTP on biological cells (prokaryotes and eukaryotes) are mediated by reactive oxygen and nitrogen species (RONS) [11,12,[59][60][61][62][63][64][65][66]. These species include hydroxyl, OH, atomic oxygen, O, singlet delta oxygen, O 2 ( 1 ∆), superoxide, O 2 − , hydrogen peroxide, H 2 O 2 , and nitric oxide, NO.…”

Treatment of Triple-Negative Breast Cancer Cells with the Canady Cold Plasma Conversion System: Preliminary Results

“…In particular, the research of CAP as a potential oncotherapeutic approach has thrived over the past decade and the mechanism is been increasingly understood [12][13][14][15][16]. It is widely reported that CAP deactivated more than 20 types of cancer in vitro by inducing apoptosis [17][18][19], cell cycle arrest [20][21][22], endoplasmic reticulum stress [23,24] and DNA damage [25][26][27]. CAP has also been shown to significantly reduce tumor volume in an in vivo murine model following s phase cell cycle arrest and apoptosis [28].…”