Cadmium induces oxidative stress and apoptosis in lung epithelial cells

IF 2.8 4区医学 Q2 TOXICOLOGY

Toxicology Mechanisms and Methods Pub Date : 2016-11-06 DOI:10.1080/15376516.2016.1223240

K. K. Kiran Kumar, M. Naveen Kumar, R. Patil, Rashmi Nagesh, Shubha M. Hegde, K. Kavya, R. Babu, G. Ramesh, S. C. Sharma

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引用次数: 40

Abstract

Abstract Cadmium (Cd) is one of the well-known highly toxic environmental and industrial pollutants. Cd first accumulates in the nucleus and later interacts with zinc finger proteins of antiapoptotic genes and inhibit the binding of transcriptional factors and transcription. However, the role of Cd in oxidative stress and apoptosis is less understood. Hence, the present study was undertaken to unveil the mechanism of action. A549 cells were treated with or without Cd and cell viability was measured by MTT assay. Treatment of cells with Cd shows reduced viability in a dose-dependent manner with IC50 of 45 μM concentration. Cd significantly induces the reactive oxygen species (ROS), lipid peroxidation followed by membrane damage with the leakage of lactate dehydrogenase (LDH). Cells with continuous exposure of Cd deplete the antioxidant super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Further, analysis of the expression of genes involved in apoptosis show that both the extrinsic and intrinsic apoptotic pathways were involved. Death receptor marker tumor necrosis factor-α (TNF-α), executor caspase-8 and pro-apoptotic gene (Bax) were induced, while antiapoptotic gene (Bcl-2) was decreased in Cd-treated cells. Fluorescence-activated cell sorting (FACS) analysis further confirms the induction of apoptosis in Cd-treated A549 cells.

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镉诱导肺上皮细胞氧化应激和凋亡

摘要镉(Cd)是众所周知的高毒性环境污染物和工业污染物之一。Cd首先在细胞核内积累，然后与抗凋亡基因的锌指蛋白相互作用，抑制转录因子的结合和转录。然而，镉在氧化应激和细胞凋亡中的作用尚不清楚。因此，本研究旨在揭示其作用机制。分别对A549细胞进行Cd处理和不Cd处理，用MTT法测定细胞活力。Cd处理后，细胞活力呈剂量依赖性降低，IC50浓度为45 μM。Cd显著诱导活性氧(ROS)和脂质过氧化，并导致乳酸脱氢酶(LDH)渗漏导致细胞膜损伤。连续暴露于Cd的细胞会消耗抗氧化超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)酶。此外，对参与细胞凋亡的基因表达的分析表明，外源性和内在凋亡途径都参与其中。死亡受体标志物肿瘤坏死因子-α (TNF-α)、执行子caspase-8和促凋亡基因(Bax)被诱导，而抗凋亡基因(Bcl-2)在cd处理的细胞中被降低。荧光活化细胞分选(FACS)分析进一步证实cd处理的A549细胞诱导凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.