Mitochondrial dysfunction, perturbations of mitochondrial dynamics and biogenesis involved in endothelial injury induced by silica nanoparticles

Guo, Caixia; Ji, Wang; Li, Jing; Ma, Ru; Li, Xiaoying; Gao, Lifang; Cao, Lige; Duan, Junchao; Zhou, Xianqing; Li, Yanbo; Sun, Zhiwei

doi:10.1016/j.envpol.2017.10.060

Cited by 116 publications

(52 citation statements)

References 66 publications

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“…SiNPs could increase the intracellular level of mitochondrial ROS, eventually resulting in the collapse of mitochondrial membrane potential and impairment in ATP synthesis, cellular respiration, and the activities of three ATPdependent enzymes (including Na + /K + -ATPase, Ca 2+ -ATPase, and Ca 2+ /Mg 2+ -ATPase), as well as an elevated intracellular calcium level. 45 In this study, the expression of ANG II and ET-1 was increased. ANG II and ET-1 are strong vasoconstrictors that may raise blood pressure and result in possible injury to blood vessels.…”

Section: 200 On 29-sep-2020supporting

confidence: 50%

Co-exposure subacute toxicity of silica nanoparticles and lead acetate on cardiovascular system

Lin

Yang

Shi

et al. 2018

IJN

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BackgroundThe harmful effects following the release of nanomaterials into environment are of great concern today.PurposeIn this study, subacute effect due to co-exposure to low-dose silica nanoparticles (SiNPs) and lead acetate (Pb) on cardiovascular system was detected in Sprague Dawley male rats.Materials and MethodsHistopathological and ultrastructural changes of heart, aortic arch and abdominal aorta were detected. Blood routine and blood biochemistry examinations were used to show the changes of blood components. The fibrinolytic and plasmin factors, inflammation-related factors and myocardial-related enzyme in serum were analysised by ELISA and Western blot assay.ResultsHistopathological and ultrastructural examination of heart, aortic arch, and abdominal aorta showed that serious damage occurred in co-exposure group (n=6/group). Blood routine examination showed that leukocytosis and thrombocytopenia increased markedly, while changes in the erythrocyte count were not obvious in the co-exposure group. The expression of alanine transaminase (ALT) decreased obviously in co-exposure group, while no significant changes were noted in the expression of aspartate aminotransferase (AST), cholesterol (CHO), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) in the co-exposure group on blood biochemistry analysis. In addition, data from ELISA analysis showed that the levels of fibrinolytic and plasmin factors, including thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), tissue-type plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and antithrombin III (AT III), were decreased, while those of human fibrinogen (FIB) and D-dimer (D2D) increased significantly in the co-exposure group. Moreover, the myocardial-related enzyme in serum, tested by ELISA, and cardiovascular-related protein expression of atrial natriuretic peptide and brain natriuretic peptide, tested by Western blot assay, was increased in the heart. Furthermore, the expression of inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) was increased in heart tissue subjected to combined exposure, which was manifested by Western blot assay, while the protein levels of angiotensin II (ANG II) and endothelin 1 were (ET-1) elevated in blood vessels in the co-exposure group.ConclusionIn conclusion, the major interactions involved in subacute toxicity due to co-exposure to low doses of SiNPs and Pb on cardiovascular system were expected to be additive and synergistic in nature. Co-exposure to SiNPs and Pb could aggravate the cardiovascular toxicity via endothelial damage, hypercoagulation, and cardiac injury in vivo.

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Section: 200 On 29-sep-2020supporting

confidence: 50%

Co-exposure subacute toxicity of silica nanoparticles and lead acetate on cardiovascular system

Lin

Yang

Shi

et al. 2018

IJN

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“…This interpretation is again consistent with the feed-forward regulatory mechanism of mitochondrial ROS-induced ROS generation during structural remodeling of mitochondria. Moreover, silica nanoparticles were reported to induce mitochondrial fragmentation in human umbilical vein endothelial cells, which was caused by dysregulation of the fission machinery proteins, ∆ Ψ m loss, and accompanied by increased mitochondrial ROS formation and decreased mtDNA copy number [ 223 ]. These studies underscore the fact that mitochondrial ultrastructure changes can be inherently part of the mechanism of action of ROS-generating chemotherapeutics.…”

Section: Modulation Of Reactive Oxygen Species By Mitochondrial Dymentioning

confidence: 99%

Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression

2018

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Mitochondria are organelles with a highly dynamic ultrastructure maintained by a delicate equilibrium between its fission and fusion rates. Understanding the factors influencing this balance is important as perturbations to mitochondrial dynamics can result in pathological states. As a terminal site of nutrient oxidation for the cell, mitochondrial powerhouses harness energy in the form of ATP in a process driven by the electron transport chain. Contemporaneously, electrons translocated within the electron transport chain undergo spontaneous side reactions with oxygen, giving rise to superoxide and a variety of other downstream reactive oxygen species (ROS). Mitochondrially-derived ROS can mediate redox signaling or, in excess, cause cell injury and even cell death. Recent evidence suggests that mitochondrial ultrastructure is tightly coupled to ROS generation depending on the physiological status of the cell. Yet, the mechanism by which changes in mitochondrial shape modulate mitochondrial function and redox homeostasis is less clear. Aberrant mitochondrial morphology may lead to enhanced ROS formation, which, in turn, may deteriorate mitochondrial health and further exacerbate oxidative stress in a self-perpetuating vicious cycle. Here, we review the latest findings on the intricate relationship between mitochondrial dynamics and ROS production, focusing mainly on its role in malignant disease.

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“…A growing evidence suggests that mitochondrial biogenesis is critically involved in nanoparticles induced injury. 25 To illustrate the effect of ZnO NPs on mitochondrial biogenesis, the mitochondrial density and mtDNA copy number were analyzed, respectively, by Mito-Tracker green staining and qPCR after the cells were incubated with ZnO NPs for 6 h. As compared to the cells in control group, the mitochondrial density of the cells treated with 25 μM ZnO NPs was increased slightly but not significantly (105% of control), while the mitochondrial densities of the cells treated with 50 and 100 μM ZnO NPs were decreased to 85% and 63% of control, respectively ( Figure 6A and B). It has been reported that mtDNA replication transcription system was activated to counteract mitochondrial oxidative respiratory chain damage under the mild oxidative stress level.…”

Section: Mitochondrial Biogenesis Was Impaired By Zno Npsmentioning

confidence: 99%

<p>Zinc Oxide Nanoparticles Induce Mitochondrial Biogenesis Impairment and Cardiac Dysfunction in Human iPSC-Derived Cardiomyocytes</p>

Li¹,

Li²,

Zhang³

et al. 2020

IJN

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Background: Zinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanomaterials in a variety of fields such as industrial, pharmaceutical, and household applications. Increasing evidence suggests that ZnO NPs could elicit unignorable harmful effect to the cardiovascular system, but the potential deleterious effects to human cardiomyocytes remain to be elucidated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been increasingly used as a promising in vitro model of cardiomyocyte in various fields such as drug cardiac safety evaluation. Herein, the present study was designed to elucidate the cardiac adverse effects of ZnO NPs and explore the possible underlying mechanism using hiPSC-CMs. Methods: ZnO NPs were characterized by transmission electron microscopy and dynamic light scattering. The cytotoxicity induced by ZnO NPs in hiPSC-CMs was evaluated by determination of cell viability and lactate dehydrogenase release. Cellular reactive oxygen species (ROS) and mitochondrial membrane potential were measured by high-content analysis (HCA). Mitochondrial biogenesis was assayed by detection of mtDNA copy number and PGC-1α pathway. Moreover, microelectrode array techniques were used to investigate cardiac electrophysiological alterations. Results: We demonstrated that ZnO NPs concentration-and time-dependently elicited cytotoxicity in hiPSC-CMs. The results from HCA revealed that ZnO NPs exposure at lowcytotoxic concentrations significantly promoted ROS generation and induced mitochondrial dysfunction. We further demonstrated that ZnO NPs could impair mitochondrial biogenesis and inhibit PGC-1α pathway. In addition, ZnO NPs at insignificantly cytotoxic concentrations were found to trigger cardiac electrophysiological alterations as evidenced by decreases of beat rate and spike amplitude. Conclusion: Our findings unveiled the potential harmful effects of ZnO NPs to human cardiomyocytes that involve mitochondrial biogenesis and the PGC-1α pathway that could affect cardiac electrophysiological function.

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Mitochondrial dysfunction, perturbations of mitochondrial dynamics and biogenesis involved in endothelial injury induced by silica nanoparticles

Cited by 116 publications

References 66 publications

Co-exposure subacute toxicity of silica nanoparticles and lead acetate on cardiovascular system

Co-exposure subacute toxicity of silica nanoparticles and lead acetate on cardiovascular system

Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression

<p>Zinc Oxide Nanoparticles Induce Mitochondrial Biogenesis Impairment and Cardiac Dysfunction in Human iPSC-Derived Cardiomyocytes</p>

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