ArticleNeuropharmacology2020
Metformin attenuates cadmium-induced neuronal apoptosis in vitro via blocking ROS-dependent PP5/AMPK-JNK signaling pathway.
Article in Neuropharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- The irony of Parkinson's disease: Converging mechanisms of redox imbalance and ferroptosis.Redox biology · 2026Review
- Cadmium-induced apoptosis via ROS/JNK pathway in chicken primary kidney cells and antagonism of taxifolin.Poultry science · 2026Article
- Integrated network toxicology and molecular docking revealed that 2-ethylhexyldiphenylphosphoric acid induces nephrotoxicity in chickens by activating the ROS/JNK pathway.Poultry science · 2026Article
- Article
- Neurotoxic mechanisms of cadmium in neurodegenerative diseases.Frontiers in cell and developmental biology · 2026Review
- Article
- Metformin Mitigates the Impact of Arsenic Exposure on the Maternal and Offspring Reproductive System of Female Mice.Biological trace element research · 2025Article
- Neuroprotective Effects of Metformin Through the Modulation of Neuroinflammation and Oxidative Stress.Cells · 2025Review
- Targeting Ferroptosis in Parkinson's: Repurposing Diabetes Drugs as a Promising Treatment.International journal of molecular sciences · 2025Review
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?International journal of molecular sciences · 2024Review
- Metformin enhances endogenous neural stem cells proliferation, neuronal differentiation, and inhibits ferroptosis through activating AMPK pathway after spinal cord injury.Journal of translational medicine · 2024Article
- Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies.Antioxidants (Basel, Switzerland) · 2024Review
- Insights into the Role of Histone Methylation in Brain Aging and Potential Therapeutic Interventions.International journal of molecular sciences · 2023Review
- RETRACTED: Beta-Caryophyllene, a Plant-Derived CB2 Receptor Agonist, Protects SH-SY5Y Cells from Cadmium-Induced Toxicity.International journal of molecular sciences · 2023Article
- Targeted Activation of HNF4α by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.Neurochemical research · 2023Article
- c-Jun N-terminal kinase signaling in cellular senescence.Archives of toxicology · 2023Review
- Neuroprotective Effect of miR-483-5p Against Cardiac Arrest-Induced Mitochondrial Dysfunction Mediated Through the TNFSF8/AMPK/JNK Signaling Pathway.Cellular and molecular neurobiology · 2023Article
- Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease.Aging and disease · 2022Article
- Cadmium induces apoptosis and autophagy in swine small intestine by downregulating the PI3K/Akt pathway.Environmental science and pollution research international · 2022Article
- Methylmercury Induces Mitochondria- and Endoplasmic Reticulum Stress-Dependent Pancreatic β-Cell Apoptosis via an Oxidative Stress-Mediated JNK Signaling Pathway.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Cadmium (Cd), a toxic environment contaminant, induces reactive oxygen species (ROS)-mediated neuronal apoptosis and consequential neurodegenerative disorders. Metformin, an anti-diabetic drug, has recently received a great attention owing to its protection against neurodegenerative diseases. However, little is known regarding the effect of metformin on Cd-induced neurotoxicity. Here we show that metformin effectively prevented Cd-evoked apoptotic cell death in neuronal cells, by suppressing Cd activation of c-Jun N-terminal kinases (JNK), which was attributed to blocking Cd inactivation of protein phosphatase 5 (PP5) and AMP-activated protein kinase (AMPK). Inhibition of JNK with SP600125, knockdown of c-Jun, or overexpression of PP5 potentiated metformin's inhibitory effect on Cd-induced phosphorylation of JNK/c-Jun and apoptosis. Activation of AMPK with AICAR or ectopic expression of constitutively active AMPKα strengthened the inhibitory effects of metformin on Cd-induced phosphorylation of JNK/c-Jun and apoptosis, whereas expression of dominant negative AMPKα weakened these effects of metformin. Metformin repressed Cd-induced ROS, thereby diminishing cell death. N-acetyl-l-cysteine enhanced the inhibitory effects of metformin on Cd-induced ROS and apoptosis. Moreover, using Mito-TEMPO, we further demonstrated that metformin attenuated Cd-induced cell death by suppressing induction of mitochondrial ROS. Taken together, these results indicate that metformin prevents mitochondrial ROS inactivation of PP5 and AMPK, thus attenuating Cd-induced JNK activation and apoptosis in neuronal cells. Our data highlight that metformin may be a promising drug for prevention of Cd-induced oxidative stress and neurodegenerative diseases.
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Registered trials
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