Calpain activation and disturbance of autophagy are induced in cortical neurons in vitro by exposure to HA/β-Ga2O3:Cr3+ nanoparticles

Lei, Yu; Wang, Cheng-Kun; Jiang, Quan; Sun, Xiaoyi; Du, Yong‐Zhong; Zhu, Yaofeng; Lu, Yuanqing

doi:10.7717/peerj.4365

Cited by 4 publications

(3 citation statements)

References 54 publications

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“…As a calcium and calmodulin-dependent protein phosphatase, calcineurin could be cleaved and activated by calpain, which increases phosphatase activity of calcineurin (Wu et al 2007 ; Zhao et al 2016 ). Calpain/calcineurin pathway also participates in pyroptosis (Zu et al 2020 ) and neuron injury (Lei et al 2018 ). Therefore, we examined whether the calpain/calcineurin pathway is involved in VMC.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of calpain reduces cell apoptosis by suppressing mitochondrial fission in acute viral myocarditis

Shi

Liu

et al. 2021

Cell Biol Toxicol

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Cardiomyocyte apoptosis is critical for the development of viral myocarditis (VMC), which is one of the leading causes of cardiac sudden death in young adults. Our previous studies have demonstrated that elevated calpain activity is involved in the pathogenesis of VMC. This study aimed to further explore the underlying mechanisms. Neonatal rat cardiomyocytes (NRCMs) and transgenic mice overexpressing calpastatin were infected with coxsackievirus B3 (CVB3) to establish a VMC model. Apoptosis was detected with flow cytometry, TUNEL staining, and western blotting. Cardiac function was measured using echocardiography. Mitochondrial function was measured using ATP assays, JC-1, and MitoSOX. Mitochondrial morphology was observed using MitoTracker staining and transmission electron microscopy. Colocalization of dynamin-related protein 1 (Drp-1) in mitochondria was examined using immunofluorescence. Phosphorylation levels of Drp-1 at Ser637 site were determined using western blotting analysis. We found that CVB3 infection impaired mitochondrial function as evidenced by increased mitochondrial ROS production, decreased ATP production and mitochondrial membrane potential, induced myocardial apoptosis and damage, and decreased myocardial function. These effects of CVB3 infection were attenuated by inhibition of calpain both by PD150606 treatment and calpastatin overexpression. Furthermore, CVB3-induced mitochondrial dysfunction was associated with the accumulation of Drp-1 in the outer membrane of mitochondria and subsequent increase in mitochondrial fission. Mechanistically, calpain cleaved and activated calcineurin A, which dephosphorylated Drp-1 at Ser637 site and promoted its accumulation in the mitochondria, leading to mitochondrial fission and dysfunction. In summary, calpain inhibition attenuated CVB3-induced myocarditis by reducing mitochondrial fission, thereby inhibiting cardiomyocyte apoptosis.

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Section: Discussionmentioning

confidence: 99%

Inhibition of calpain reduces cell apoptosis by suppressing mitochondrial fission in acute viral myocarditis

Shi

Liu

et al. 2021

Cell Biol Toxicol

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“…Decrease in viability and increase of apoptosis were observed in primary cortical neurons after incubation with gallium trioxide NPs modified with chromium ions and hyaluronic acid (HA/Ga 2 O 3 :Cr 3+ NPs). The toxicity was explained by activation of calpain and disruption autophagy signaling [91]. Also no toxicity was observed for 145 nm tungsten carbide particles (WC) in any of the cell lines tested including oligodendrocytes, rat primary neurons, rat primary astroglial cells, however, doping WC NPs with cobalt (WC -Co) resulted in an increase in the toxicity.…”

Section: Toxicity In Vitromentioning

confidence: 99%

Toxicity of metallic nanoparticles in the central nervous system

Sawicki

Czajka

Matysiak‐Kucharek

et al. 2019

Nanotechnology Reviews

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Metallic nanoparticles due to their small size and unique physico-chemical characteristics have found excellent applications in various branches of industry and medicine. Therefore, for many years a growing interest has been observed among the scientific community in the improvement of our understanding of the impact of nanoparticles on the living organisms, especially on humans. Considering the delicate structure of the central nervous systemit is one of the organs most vulnerable to the adverse effects of metallic nanoparticles. For that reason, it is important to identify the modes of exposure and understand the mechanisms of the effect of nanoparticles on neuronal tissue. In this review, an attempt is undertaken to present current knowledge about metallic nanoparticles neurotoxicity based on the selected scientific publications. The route of entry of nanoparticles is described, as well as their distribution, penetration through the cell membrane and the blood-brain barrier. In addition, a study on the neurotoxicity in vitro and in vivo is presented, as well as some of the mechanisms that may be responsible for the negative effects of metallic nanoparticles on the central nervous system. Graphical abstract: This review summarizes the current knowledge on the toxicity of metallic NPs in the brain and central nervous system of the higher vertebrates.

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“…A growing body of evidence has linked NM-induced cytoskeletal disruption with autophagy effects. Since the actin cytoskeleton participates in the formation and fusion of autophagosomes with lysosomes, any damage to the actin cytoskeleton can impair the above process, ultimately resulting in blockade of autophagic flux [126,150]. Graphite carbon nanofibers (GCNF) can trigger apoptosis in human lung cells through excessive autophagosomes accumulation that resulted from cytoskeleton disruption-mediated autophagic flux blockade rather than autophagy induction [151].…”

Section: Cytoskeleton Disruptionmentioning

confidence: 99%

Nanomaterial-mediated autophagy: coexisting hazard and health benefits in biomedicine

Feng

Zhang

et al. 2020

Part Fibre Toxicol

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Background Widespread biomedical applications of nanomaterials (NMs) bring about increased human exposure risk due to their unique physicochemical properties. Autophagy, which is of great importance for regulating the physiological or pathological activities of the body, has been reported to play a key role in NM-driven biological effects both in vivo and in vitro. The coexisting hazard and health benefits of NM-mediated autophagy in biomedicine are nonnegligible and require our particular concerns. Main body We collected research on the toxic effects related to NM-mediated autophagy both in vivo and in vitro. Generally, NMs can be delivered into animal models through different administration routes, or internalized by cells through different uptake pathways, exerting varying degrees of damage in tissues, organs, cells, and organelles, eventually being deposited in or excreted from the body. In addition, other biological effects of NMs, such as oxidative stress, inflammation, necroptosis, pyroptosis, and ferroptosis, have been associated with autophagy and cooperate to regulate body activities. We therefore highlight that NM-mediated autophagy serves as a double-edged sword, which could be utilized in the treatment of certain diseases related to autophagy dysfunction, such as cancer, neurodegenerative disease, and cardiovascular disease. Challenges and suggestions for further investigations of NM-mediated autophagy are proposed with the purpose to improve their biosafety evaluation and facilitate their wide application. Databases such as PubMed and Web of Science were utilized to search for relevant literature, which included all published, Epub ahead of print, in-process, and non-indexed citations. Conclusion In this review, we focus on the dual effect of NM-mediated autophagy in the biomedical field. It has become a trend to use the benefits of NM-mediated autophagy to treat clinical diseases such as cancer and neurodegenerative diseases. Understanding the regulatory mechanism of NM-mediated autophagy in biomedicine is also helpful for reducing the toxic effects of NMs as much as possible.

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Calpain activation and disturbance of autophagy are induced in cortical neurons in vitro by exposure to HA/β-Ga₂O₃:Cr³⁺ nanoparticles

Cited by 4 publications

References 54 publications

Inhibition of calpain reduces cell apoptosis by suppressing mitochondrial fission in acute viral myocarditis

Inhibition of calpain reduces cell apoptosis by suppressing mitochondrial fission in acute viral myocarditis

Toxicity of metallic nanoparticles in the central nervous system

Nanomaterial-mediated autophagy: coexisting hazard and health benefits in biomedicine

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