Genes (Sep 2022)

Estimation of Metabolic Effects upon Cadmium Exposure during Pregnancy Using Tensor Decomposition

  • Yuki Amakura,
  • Y-h. Taguchi

Journal volume & issue
Vol. 13, no. 1698
p. 1698


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A simple tensor decomposition model was applied to the liver transcriptome analysis data to elucidate the cause of cadmium-induced gene overexpression. In addition, we estimated the mechanism by which prenatal Cd exposure disrupts insulin metabolism in offspring. Numerous studies have reported on the toxicity of Cd. A liver transcriptome analysis revealed that Cd toxicity induces intracellular oxidative stress and mitochondrial dysfunction via changes in gene expression, which in turn induces endoplasmic reticulum-associated degradation via abnormal protein folding. However, the specific mechanisms underlying these effects remain unknown. In this study, we found that Cd-induced endoplasmic reticulum stress may promote increased expression of tumor necrosis factor-α (TNF-α). Based on the high expression of genes involved in the production of sphingolipids, it was also found that the accumulation of ceramide may induce intracellular oxidative stress through the overproduction of reactive oxygen species. In addition, the high expression of a set of genes involved in the electron transfer system may contribute to oxidative stress. These findings allowed us to identify the mechanisms by which intracellular oxidative stress leads to the phosphorylation of insulin receptor substrate 1, which plays a significant role in the insulin signaling pathway.