Prevention of cell death by the zinc ion chelating agent TPEN in cultured PC12 cells exposed to Oxygen–Glucose Deprivation (OGD)

Zhao, Lei; Huang, Yue-yang; Wang, Yuxiang; Wang, Honggang; Dèng, Fēi; Heng, Bin; Xie, Lai-Hua; Liu, Yanqiang

doi:10.1016/j.jtemb.2015.03.003

Cited by 12 publications

(6 citation statements)

References 40 publications

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“…41,42 Liu et al found that the application of Zn 2+ chelator TPEN can reduce PC12 cells death through glutamate signaling pathway and voltage-dependent outward potassium current changes in oxygen and glucose deprivation model. 43 In addition, Cho et al reported that subcutaneous injection of TPEN significantly reduced neuronal apoptosis in the brain by interfering with caspase-dependent apoptosis pathways in P7 rats. 44 Consistent with these studies, we found that downregulation of Zn 2+ by TPEN attenuated ketamine-induced neuronal apoptosis, while upregulation of Zn 2+ increased neuronal apoptosis in the GCL of rat retina.…”

Section: Discussionmentioning

confidence: 99%

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

Zhang

Sun

et al. 2020

CNS Neurosci Ther

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Aims During early development, laminin degradation contributes to the death of neurons. This study aims to investigate the role and regulation of laminin in ketamine‐induced apoptosis. Methods We performed terminal deoxynucleotidyl transferase biotin‐dUTP nick end labeling (TUNEL) and immunohistochemical assays to investigate the roles of the non‐integrin laminin receptor, matrix metalloproteinase 9 (MMP9) in ketamine‐induced neuronal apoptosis. In situ zymography, Western blot, and immunofluorescence were used to explore the relationships between laminin, MMP9 activity, and Zn2+. Experiments were performed using whole‐mount retinas dissected from Sprague Dawley rats. Results The TUNEL and immunohistochemical assays indicated that ketamine‐induced neuronal apoptosis in early developing rat retina. Blockade of non‐integrin laminin receptor promoted ketamine‐induced apoptosis, while non‐integrin laminin receptor activation attenuated ketamine‐induced apoptosis. Ketamine‐induced laminin degradation, possibly by enhancing the activity of MMP9. MMP9 inhibition reduced ketamine‐induced apoptosis by reducing laminin degradation. Downregulation of Zn2+ attenuated the increased MMP9 activity, laminin degradation caused by ketamine and significantly reduced ketamine‐induced neuronal apoptosis. Conclusion Laminin degradation by MMP9 promoted ketamine‐induced neuronal apoptosis in early developing rat retina. The non‐integrin laminin receptor may be a pathway involved in ketamine‐induced apoptosis. Zn2+ downregulation may play a protective role against ketamine‐induced neuronal apoptosis through inhibiting MMP9 activity.

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Section: Discussionmentioning

confidence: 99%

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

Zhang

Sun

et al. 2020

CNS Neurosci Ther

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“…In contrast, based on experiments performed with neuronal tissues, it is believed that rising zinc levels increase hypoxia-mediated cell death occurring during tissue ischemia (120,189). Correspondingly, this effect can be reduced by the Zn 2+ chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) (108,204).…”

Section: Fig 8 Measurement Of Freementioning

confidence: 99%

The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus

Gerber

Rutter

2017

Antioxidants & Redox Signaling

508

335

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Loss of normal beta-cell function, rather than total mass, is increasingly considered to be the major driver for impaired insulin secretion in diabetes. Better understanding of the role of oxidative changes, its modulation by genes involved in disease risk, and effects on beta-cell identity may facilitate the development of new therapeutic strategies to this disease. Antioxid. Redox Signal. 26, 501-518.

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“…However, in situations of cellular stress, these effects are probably shifted in favour of lower zinc concentrations, since the constitutively high concentrations of zinc in islet cells may exert an additive stress to the cell. From observations in neuronal tissues, where the interplay of hypoxic injury and zinc-mediated modulation of cell death has been studied extensively, it is known that zinc chelation by TPEN decreases apoptosis and cell death induced by oxygen and glucose deprivation ( Liu et al 2015 , Wang et al 2015 , Zhang et al 2017 ). This might also be true for pancreatic islet cells with a very high intracellular zinc content.…”

Section: Discussionmentioning

confidence: 99%

Lack of ZnT8 protects pancreatic islets from hypoxia- and cytokine-induced cell death

Karsai

Zuellig

Lehmann

et al. 2022

Journal of Endocrinology

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Pancreatic β-cells depend on the well-balanced regulation of cytosolic zinc concentrations, providing sufficient zinc ions for the processing and storage of insulin, but avoiding toxic effects. The zinc transporter ZnT8, encoded by SLC30A8, is a key player regarding islet cell zinc homeostasis, and polymorphisms in this gene are associated with altered type 2 diabetes susceptibility in man. The objective of this study was to investigate the role of ZnT8 and zinc in situations of cellular stress as hypoxia or inflammation. Isolated islets of wild-type and global ZnT8-/- mice were exposed to hypoxia or cytokines and cell death was measured. To explore the role of changing intracellular Zn2+ concentrations, wild-type islets were exposed to different zinc concentrations using zinc chloride or the zinc chelator N,N,N′,N′-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN). Hypoxia or cytokine (TNFα, IFNγ, IL1β) treatment induced islet cell death, but to a lesser extent in islets from ZnT8-/- mice, which were shown to have a reduced zinc content. Similarly, chelation of zinc with TPEN reduced cell death in wild-type islets treated with hypoxia or cytokines, whereas increased zinc concentrations aggravated the effects of these stressors. This study demonstrates a reduced rate of cell death in islets from ZnT8-/- mice as compared to wild-type islets when exposed to two distinct cellular stressors, hypoxia or cytotoxic cytokines. This protection from cell death is, in part, mediated by a reduced zinc content in islet cells of ZnT8-/- mice. These findings may be relevant for altered diabetes burden in carriers of risk SLC30A8 alleles in man.

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Prevention of cell death by the zinc ion chelating agent TPEN in cultured PC12 cells exposed to Oxygen–Glucose Deprivation (OGD)

Cited by 12 publications

References 40 publications

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

Laminin degradation by matrix metalloproteinase 9 promotes ketamine‐induced neuronal apoptosis in the early developing rat retina

The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus

Lack of ZnT8 protects pancreatic islets from hypoxia- and cytokine-induced cell death

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