Graduate School of Science and Engineering, Chuo University, Tokyo 112-8551, Japan.
Department of Physics, Chuo University, Tokyo 112-8551, Japan.
Genes (Basel). 2022 Sep 22;13(10):1698. doi: 10.3390/genes13101698.
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.
采用一种简单的张量分解模型对肝脏转录组分析数据进行了分析，以阐明镉诱导基因过表达的原因。此外，我们还估计了产前 Cd 暴露破坏后代胰岛素代谢的机制。许多研究都报道了 Cd 的毒性。肝脏转录组分析表明，Cd 毒性通过基因表达的变化诱导细胞内氧化应激和线粒体功能障碍，进而通过异常蛋白质折叠诱导内质网相关降解。然而，这些影响的确切机制尚不清楚。在本研究中，我们发现 Cd 诱导的内质网应激可能会促进肿瘤坏死因子-α（TNF-α）的表达增加。基于涉及鞘脂类物质生成的基因的高表达，还发现神经酰胺的积累可能通过过量产生活性氧物质引起细胞内氧化应激。此外，一组涉及电子传递系统的基因的高表达可能有助于氧化应激。这些发现使我们能够确定细胞内氧化应激导致胰岛素受体底物 1 磷酸化的机制，该磷酸化在胰岛素信号通路中起着重要作用。
