ArticleThe international journal of biochemistry & cell biology2020
Cadmium induces mitochondrial ROS inactivation of XIAP pathway leading to apoptosis in neuronal cells.
Article in The international journal of biochemistry & cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- MDM2-GPX4-ferroptosis regulatory axis exerts neurotoxic effects in intracerebral hemorrhage.Neural regeneration research · 2026Article
- Nanomolar Cadmium Disrupts Neurotransmitter Release Timing via a ROS-dependent Mechanism at the Mouse Neuromuscular Junction: Modulation by Nanomolar ZnNeurochemical research · 2026Article
- X-Linked Inhibitor of Apoptosis Protein (XIAP) Contributes to ERK1/2-Mediated Anoikis Resistance in Hepatocellular Carcinoma.MedComm - Oncology · 2026Article
- Cadmium Impairs Human GnRH Neuron Development: Mechanistic Insights into Reproductive Dysfunction.International journal of molecular sciences · 2026Article
- Dexmedetomidine attenuates Alzheimer's pathogenesis by targeting the ROS-mediated XIAP-MDM2-p53 signaling axis.Frontiers in pharmacology · 2026Article
- Pathological Interplay of ROS With Myofibroblasts: An Impediment to Corneal Restitution.Oxidative medicine and cellular longevity · 2026Review
- Neurotoxic mechanisms of cadmium in neurodegenerative diseases.Frontiers in cell and developmental biology · 2026Review
- Hesperidin/Salinomycin Combination; a Natural Product for Deactivation of the PI3K/Akt Signaling Pathway and Anti-Apoptotic Factors in KG1a Cells.Journal of fluorescence · 2025Article
- Neuroprotective Effects of Morin Against Cadmium- and Arsenic-Induced Cell Damage in PC12 Neurons.Biological trace element research · 2025Article
- Inflammation in Metal-Induced Neurological Disorders and Neurodegenerative Diseases.Biological trace element research · 2024Review
- Rhein suppresses African swine fever virus replication in vitro via activating the caspase-dependent mitochondrial apoptosis pathway.Virus research · 2023Article
- Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia.Journal of cellular and molecular medicine · 2023Article
- Nano-selenium Alleviates Cadmium-Induced Mouse Leydig Cell Injury, via the Inhibition of Reactive Oxygen Species and the Restoration of Autophagic Flux.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Zinc Chloride Can Mitigate the Alterations in Metallothionein and Some Apoptotic Proteins Induced by Cadmium Chloride in Mice Hepatocytes: A Histological and Immunohistochemical Study.Journal of toxicology · 2023Article
- The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation.Frontiers in cellular neuroscience · 2023Review
- DSF/Cu induces antitumor effect against diffuse large B-cell lymphoma through suppressing NF-κB/BCL6 pathways.Cancer cell international · 2022Article
- Long Non-coding RNA Peg13 Alleviates Hypoxic-Ischemic Brain Damage in Neonatal Mice via miR-20a-5p/XIAP Axis.Neurochemical research · 2022Article
- Dysfunction of X-linked inhibitor of apoptosis protein (XIAP) triggers neuropathological processes via altered p53 activity in Huntington's disease.Progress in neurobiology · 2021Article
- Downregulation of miR-181a-5p alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage by directly targeting XIAP.Journal of geriatric cardiology : JGC · 2021Article
- 2,5-Hexanedione induced apoptosis in rat spinal cord neurons and VSC4.1 cells via the proNGF/p75NTR and JNK pathways.Bioscience reports · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Cadmium (Cd), a heavy metal pollutant, contributes to neurodegenerative disorders. Recently, we have demonstrated that Cd induction of reactive oxygen species (ROS) causes apoptosis in neuronal cells. Whether X-linked inhibitor of apoptosis protein (XIAP) is involved in Cd-induced ROS-dependent neuronal apoptosis remains unclear. Here, we show that Cd-induced ROS reduced the expression of XIAP, which resulted in up-regulation of murine double minute 2 homolog (MDM2) and down-regulation of p53, leading to apoptosis in PC12 cells and primary neurons. Inhibition of MDM2 with Nutlin-3a reversed Cd-induced reduction of p53 and substantially rescued cells from excess ROS-dependent death. Overexpression of XIAP protected against Cd induction of ROS-dependent neuronal apoptosis. Inhibition of XIAP by Embelin strengthened Cd-induced ROS and apoptosis in the cells. Furthermore, we found that Cd inactivation of XIAP pathway was attributed to Cd induction of mitochondrial ROS, as evidenced by using a mitochondrial superoxide indicator MitoSOX and a mitochondria-targeted antioxidant Mito-TEMPO. Taken together, these results indicate that Cd induces mitochondrial ROS inactivation of XIAP-MDM2-p53 pathway leading to apoptosis in neuronal cells. Our findings suggest that activators of XIAP or modulation of XIAP-MDM2-p53 pathway by antioxidants may be exploited for the prevention of Cd-induced oxidative stress and neurodegenerative diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.