Silver nanoparticle-induced cell damage via impaired mtROS-JNK/MnSOD signaling pathway.

IF 3.2 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics

Toxicology Mechanisms and Methods Pub Date : 2024-09-01 Epub Date: 2024-05-13 DOI:10.1080/15376516.2024.2350595

Mei Jing Piao, Kyoung Ah Kang, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Jin Won Hyun

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引用次数: 0

Abstract

This study investigated the mechanism of silver nanoparticle (AgNP) cytotoxicity from a mitochondrial perspective. The effect of AgNP on manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, against oxidative stress has not been studied in detail. We demonstrated that AgNP decreased MnSOD mRNA level, protein expression, and activity in human Chang liver cells in a time-dependent manner. AgNP induced the production of mitochondrial reactive oxygen species (mtROS), particularly superoxide anion. AgNP was found to increase mitochondrial calcium level and disrupt mitochondrial function, leading to reduced ATP level, succinate dehydrogenase activity, and mitochondrial permeability. AgNP induced cytochrome c release from the mitochondria into the cytoplasm, attenuated the expression of the anti-apoptotic proteins phospho Bcl-2 and Mcl-1, and induced the expression of the pro-apoptotic proteins Bim and Bax. In addition, c-Jun N-terminal kinase (JNK) phosphorylation was significantly increased by AgNP. Treatment with elamipretide (a mitochondria-targeted antioxidant) and SP600125 (a JNK inhibitor) showed the involvement of MnSOD and JNK in these processes. These results indicated that AgNP damaged human Chang liver cells by destroying mitochondrial function through the accumulation of mtROS.

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银纳米粒子通过受损的 mtROS-JNK/MnSOD 信号通路诱导细胞损伤。

本研究从线粒体的角度研究了银纳米粒子（AgNP）的细胞毒性机制。AgNP对线粒体抗氧化酶锰超氧化物歧化酶（MnSOD）的影响尚未得到详细研究。我们证实，AgNP 会降低人 Chang 肝细胞中 MnSOD 的 mRNA 水平、蛋白表达量和活性，且呈时间依赖性。AgNP 诱导线粒体活性氧（mtROS）的产生，尤其是超氧阴离子。研究发现，AgNP 会增加线粒体钙水平并破坏线粒体功能，导致 ATP 水平、琥珀酸脱氢酶活性和线粒体通透性降低。AgNP 可诱导细胞色素 c 从线粒体释放到细胞质中，降低抗凋亡蛋白 phospho Bcl-2 和 Mcl-1 的表达，并诱导促凋亡蛋白 Bim 和 Bax 的表达。此外，AgNP 还显著增加了 c-Jun N 端激酶（JNK）的磷酸化。线粒体靶向抗氧化剂 Elamipretide 和 JNK 抑制剂 SP600125 的处理表明，MnSOD 和 JNK 参与了这些过程。这些结果表明，AgNP 通过 mtROS 的积累破坏线粒体功能，从而损害人 Chang 肝细胞。

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 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

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.