二氧化钛纳米颗粒(TiO2-NP)暴露过程中人体循环蛋白质组相互作用、氧化应激相关信号传导和心血管影响

IF 3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular omics Pub Date : 2025-04-09 DOI:10.1039/d4mo00205a
Gobichettipalayam Balasubramaniam Maadurshni, Balamurali Mahalakshmi, Manikandan Nagarajan, Jeganathan Manivannan
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引用次数: 0

摘要

越来越多的接触纳米粒子引起了人们对其毒性的担忧。顺便说一句,活性氧(ROS)是由于纳米颗粒的物理化学特性和与细胞内元素(主要是酶)的相互作用而产生的,从而导致氧化应激。在这种情况下,氧化应激引起的二氧化钛纳米颗粒(TiO2-NPs)对心血管系统的毒性程度尚未得到彻底的研究。最初,采用凝胶/无标签蛋白质组学(nLC-HRMS/MS)方法检测人血清蛋白相互作用和冠状蛋白组成。此外,在内皮细胞(大鼠主动脉细胞)和成心肌细胞(H9c2)培养的同时,进行了不同的氧化应激实验(超氧化物、总ROS、线粒体ROS和脂质过氧化)和细胞应激实验(凋亡、内质网应激、线粒体功能障碍、自噬和肥大)。此外,还进行了表达研究(RT-qPCR和免疫荧光)、激酶信号传导和sirna介导的基因敲除(NOX2和XO)研究。此外,对心脏抗氧化酶(SOD和CAT)和代谢组学途径(1H NMR)的影响证实了氧化应激在心脏毒性中的作用。目前的结果表明,通过激活半胱天冬酶3和9,细胞毒性呈剂量依赖性增加。这种剂量依赖性的增加及其与心血管应激信号(ET-1和Ang-II)的协同关系突出了氧化应激在纳米颗粒毒性中的重要作用。总之,本研究通过建立氧化还原系统和分子应激途径在tio2 - nps诱导的心脏毒性中的作用之间的联系,扩大了我们对与人类暴露相关的确切健康风险的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Human circulatory proteome interaction, oxidative stress-associated signalling and cardiovascular implications during titanium dioxide nanoparticle (TiO2-NP) exposure.

The increasing exposure to nanoparticles raises a concern over their toxicity. Incidentally, reactive oxygen species (ROS) are produced as a result of the nanoparticle's physicochemical characteristics and interactions with intracellular elements, primarily enzymes, leading to oxidative stress. In this context, the extent of oxidative stress resulting from the toxicity of titanium dioxide nanoparticles (TiO2-NPs) on the cardiovascular system has not yet been thoroughly investigated. Initially, the gel/label-free proteomics (nLC-HRMS/MS) method was used to examine human serum protein interaction and corona composition. Furthermore, different oxidative stress assays (superoxide, total ROS, mitochondrial ROS, and lipid peroxidation) and cell stress assays (apoptosis, ER stress, mitochondrial dysfunction, autophagy, and hypertrophy) were performed in conjunction with endothelial (rat aortic cells) and cardiomyoblast (H9c2) cell cultures. In addition, expression studies (RT-qPCR and immunofluorescence), kinase signalling, and siRNA-mediated gene knockout (NOX2 and XO) studies were conducted. Alongside, in ovo effects on the heart's antioxidant enzymes (SOD and CAT) and metabolomic pathways (1H NMR) confirmed the involvement of oxidative stress in cardiotoxicity. The present results demonstrate a dose-dependent increase in cytotoxicity via the activation of caspase 3 and 9. The dose-dependent increase and its synergistic relationship with cardiovascular stress signalling (ET-1 and Ang-II) highlight the significant role of oxidative stress in nanoparticle toxicity. In summary, this study expands our understanding of the precise health risks associated with human exposure by establishing a connection between the role of the redox system and molecular stress pathways in TiO2-NPs-induced cardiotoxicity.

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来源期刊
Molecular omics
Molecular omics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
5.40
自引率
3.40%
发文量
91
期刊介绍: Molecular Omics publishes high-quality research from across the -omics sciences. Topics include, but are not limited to: -omics studies to gain mechanistic insight into biological processes – for example, determining the mode of action of a drug or the basis of a particular phenotype, such as drought tolerance -omics studies for clinical applications with validation, such as finding biomarkers for diagnostics or potential new drug targets -omics studies looking at the sub-cellular make-up of cells – for example, the subcellular localisation of certain proteins or post-translational modifications or new imaging techniques -studies presenting new methods and tools to support omics studies, including new spectroscopic/chromatographic techniques, chip-based/array technologies and new classification/data analysis techniques. New methods should be proven and demonstrate an advance in the field. Molecular Omics only accepts articles of high importance and interest that provide significant new insight into important chemical or biological problems. This could be fundamental research that significantly increases understanding or research that demonstrates clear functional benefits. Papers reporting new results that could be routinely predicted, do not show a significant improvement over known research, or are of interest only to the specialist in the area are not suitable for publication in Molecular Omics.
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