{"title":"Human circulatory proteome interaction, oxidative stress-associated signalling and cardiovascular implications during titanium dioxide nanoparticle (TiO<sub>2</sub>-NP) exposure.","authors":"Gobichettipalayam Balasubramaniam Maadurshni, Balamurali Mahalakshmi, Manikandan Nagarajan, Jeganathan Manivannan","doi":"10.1039/d4mo00205a","DOIUrl":null,"url":null,"abstract":"<p><p>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 (TiO<sub>2</sub>-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 <i>via</i> 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 TiO<sub>2</sub>-NPs-induced cardiotoxicity.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular omics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1039/d4mo00205a","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
Molecular omicsBiochemistry, 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.