Ferritinophagy Mediated by Oxidative Stress-Driven Mitochondrial Damage Is Involved in the Polystyrene Nanoparticles-Induced Ferroptosis of Lung Injury

Yang, Sheng; Zhang, Tianyi; Ge, Yiling; Cheng, Yanping; Yin, Lihong; Pu, Yuepu; Chen, Zaozao; Liang, Geyu

doi:10.1021/acsnano.3c07255

Cited by 9 publications

(3 citation statements)

References 67 publications

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“…These changes led to the uncoupling of oxidative phosphorylation, with accompanying calcium ion and cytochrome c efflux, causing a series of mitochondrial dysfunctions, including oxidative phosphorylation damage, decreased kinase activity, and oxidative damage. 26 Therefore, improving mitochondrial function was vital in myocardial injury after hemorrhagic shock.…”

Section: Discussionmentioning

confidence: 99%

The New Nano-Resuscitation Solution (TPP-MR) Attenuated Myocardial Injury in Hemorrhagic Shock Rats by Inhibiting Ferroptosis

Tan,

She,

Wang

et al. 2024

IJN

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Background Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer’s (AR) and Lactate Ringer’s solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear. Methods The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury. Results TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats’ survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity. Conclusion The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis.

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Section: Discussionmentioning

confidence: 99%

The New Nano-Resuscitation Solution (TPP-MR) Attenuated Myocardial Injury in Hemorrhagic Shock Rats by Inhibiting Ferroptosis

Tan,

She,

Wang

et al. 2024

IJN

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“…Deferoxamine mesylate (DFOM) is an iron-chelating agent (combining Fe (III) and many other metal cations) that is widely used to reduce the accumulation and deposition of iron tissues. DFOM can upregulate HIF-1α level, with good antioxidant activity 24,25 . The expression levels of Mettl3 and HIF-1α decreased as the concentration of DFOM decreased (Fig.…”

Section: Hif-1α Can Recruit Mettl3 As the Target To Increase Its Expr...mentioning

confidence: 99%

METTL3 drives heart failure by regulating Spp1 and Fos m6A modification in myocardial infarction

Cheng,

Li,

Zhou

et al. 2024

Preprint

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While m6A modification has been reported in myocardial infarction (MI), the detailed mechanism by which METTL3 regulates the progression of the disease has not yet been elucidated, and it remains unclear why m6A modification increases after MI. Through MeRIP-seq and extensive bioinformatics analysis, the target genes SPP1 and FOS with the most significant m6A modification and differential expression in MI were screened. We successfully constructed heart specific Mettl3 knockout mice (Mettl3CKO) to verify that METTL3 promotes the deterioration of cardiac function after MI. We performed complementary molecular methods to assess protein quantity and interactions to identify mechanisms regulating this response. We manipulated select molecular pathways using both genetic and pharmacological methods to validate these mechanisms. Here, we showed that METTL3 exerted methyltransferase activity-dependent functions in gene regulation in MI, and a significant transcription factor HuR assisted the function of METTL3. and demonstrated that METTL3 was critical for the promotion of heart failure after MI. More specifically, METTL3 directly interacted with HuR through its nuclear localization domain in the cell nucleus under normoxia condition. When hypoxia developed, METTL3 separated from HuR and deposited m6A into 5’UTR of Spp1 and Fos mRNA to maintain their stability. In contrast, HuR bound to the ARE domain of 3’UTR of Spp1 and Fos mRNA to take them to the cytosol, maintaining their stability. Moreover, HIF-1α directly interacted with the HRE domain of Mettl3 to promote its transcription, and HuR bound to the ARE domain of 3’UTR of Mettl3 mRNA to maintain its stability to promote following translation. Collectively, our studies revealed previously unappreciated functions of METTL3 with the help of HuR, and a direct target of HIF-1α under normoxia condition, which together contribute to its essential function in MI, suggesting therapeutic potential for targeting the METTL3/HuR/Spp1(Fos) mRNA axis.

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“…Pertaining to iron metabolism, cells undergoing ferroptosis exhibit modifications in the processes of iron uptake, storage, utilization, and efflux, culminating in cellular iron overload [14,15]. Researchers have addressed the issue of elevated cellular iron levels by regulating proteins such as transferrin receptor, ferritin, ferroportin1, and employing iron chelators like deferriamine [14,16,17]. In the realm of cellular lipid metabolism, the peroxidation of polyunsaturated fatty acids into PUFA-PLs represents a pivotal pathway in ferroptosis [4].…”

Section: Mechanism and Pathway Of Ferroptosismentioning

confidence: 99%

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Xu,

Jia,

et al. 2024

Antioxidants

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Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain diseases, traumatic brain injury, epilepsy, depression, and more. The involved pathogenesis is notably intricate and diverse. Ferroptosis and neuroinflammation play pivotal roles in elucidating the causes of cognitive impairment stemming from these diseases. Given the concurrent occurrence of ferroptosis and neuroinflammation due to metabolic shifts such as iron and ROS, as well as their critical roles in central nervous disorders, the investigation into the co-regulatory mechanism of ferroptosis and neuroinflammation has emerged as a prominent area of research. This paper delves into the mechanisms of ferroptosis and neuroinflammation in central nervous disorders, along with their interrelationship. It specifically emphasizes the core molecules within the shared pathways governing ferroptosis and neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, and how different immune cells and structures contribute to cognitive dysfunction through these mechanisms. Researchers’ findings suggest that ferroptosis and neuroinflammation mutually promote each other and may represent key factors in the progression of central neurological disorders. A deeper comprehension of the common pathway between cellular ferroptosis and neuroinflammation holds promise for improving symptoms and prognosis related to central neurological disorders.

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Ferritinophagy Mediated by Oxidative Stress-Driven Mitochondrial Damage Is Involved in the Polystyrene Nanoparticles-Induced Ferroptosis of Lung Injury

Cited by 9 publications

References 67 publications

The New Nano-Resuscitation Solution (TPP-MR) Attenuated Myocardial Injury in Hemorrhagic Shock Rats by Inhibiting Ferroptosis

The New Nano-Resuscitation Solution (TPP-MR) Attenuated Myocardial Injury in Hemorrhagic Shock Rats by Inhibiting Ferroptosis

METTL3 drives heart failure by regulating Spp1 and Fos m6A modification in myocardial infarction

The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

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