GSK-3β-mediated regulation of cadmium-induced cell death and survival

Seungwoo Kim1, Hyosoon Cheon1, Sam-Moon Kim1

  • 11Division of Brain Diseases, Center for Biomedical Science, National Institute of Health, Center for Disease Control & Prevention, Osong Health Technology Administration Complex, 187, Osongsaengmyeong2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, South Korea.

Abstract

Insights

Cadmium exposure induces endoplasmic reticulum stress and activates Akt/GSK-3β signaling, which plays a role in neuronal cell survival. This study investigates the specific mechanisms of cadmium-induced neuronal cell death.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Toxicology

Background:

  • Cadmium (Cd) exposure is known to affect PI3-kinase/Akt phosphorylation and GSK-3β activity.
  • The precise mechanisms of Cd-induced endoplasmic reticulum (ER) stress in neuronal cells require further investigation.

Purpose of the Study:

  • To elucidate the role of GSK-3β in cadmium-induced neuronal cell death.
  • To investigate the downstream signaling pathways involved in Cd toxicity.

Main Methods:

  • SH-SY5Y human neuroblastoma cells were treated with cadmium (Cd) after pre-treatment with BAPTA-AM and wortmannin.
  • Apoptosis was assessed using DAPI and PI staining.
  • Western blotting was used to analyze protein expression and phosphorylation levels of Akt and GSK-3β.

Main Results:

  • Cd treatment induced ER stress, indicated by increased GRP78 expression.
  • Cd significantly increased the phosphorylation of Akt and GSK-3β in a time-dependent manner.
  • GSK-3β knockdown exacerbated Cd-induced apoptosis, suggesting a protective role.

Conclusions:

  • The Akt/GSK-3β signaling pathway activated by Cd contributes to neuronal cell survival.
  • GSK-3β plays a critical role in modulating neuronal responses to cadmium toxicity.

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