Polystyrene microplastics trigger hepatocyte apoptosis and abnormal glycolytic flux via ROS-driven calcium overload

Human health could be affected by the spread of microplastics in the food chain. Our previous research has indicated that microplastics accumulated in the liver and subsequently induce oxidative damage. However, the molecular events linking oxidative stress to calcium ion (CA²⁺) signaling during microplastics stress remains elusive. The present research demonstrated that up-regulation of Orai 1 and stromal interaction molecule 1 (Stim1) expression participated in the microplastics-triggered CA²⁺ overload, accompanied with the down-regulation of arcoplasmic reticulum CA²⁺ ATPase (SERCA). However, when the protein expression of Stim1/SERCA is restored, microplastics-induced CA²⁺ overload is ameliorated. Further analysis revealed that inhibiting the microplastics-induced CA²⁺ overload was integral to prevent hepatocyte Apoptosis and S phase arrest in the L02 hepatocyte. Simultaneously, we observed that inhibiting microplastics-evoked Reactive Oxygen Species (ROS) could alleviate CA²⁺ overload via reversing expression of store-operated CA²⁺ channels (SOCs). These changes were accompanied by restoration of glycolytic flux, likely due to the regulation of AMP-activated protein kinase (AMPK)-PGC-1α signaling. Our findings highlight the role of SOCs at microplastics-evoked ROS in CA²⁺ overload, and its a crucial step in triggering hepatocyte death. Collectively, this study reveals a regulatory paradigm that links ROS with AMPK and CA²⁺ signaling in microplastics-triggered hepatotoxicity.

Calcium ion; Glycolytic flux; Hepatotoxicity; Microplastics; Reactive oxygen species (ROS).