Mar 27, 2020

Metformin attenuates cadmium-induced neuronal apoptosis in vitro via blocking ROS-dependent PP5/AMPK-JNK signaling pathway

Neuropharmacology
Xiaoling ChenLong Chen

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 metfor...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Gene Knockdown Techniques
Protein Expression
Protein Overexpression
Neurotoxicity Syndromes
MAP2K1 protein, human
Neurons
Signal Pathways
Cadmium sulfide
Acetylcysteine
Oxidative Stress

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Astrocytes and Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Related Papers

The New England Journal of Medicine
C J Bailey, R C Turner
Diabetes Care
Z T Bloomgarden
Endocrine Research
Michael StumvollStephan Matthaei
© 2020 Meta ULC. All rights reserved