Arsenite exposure potentiates apoptosis-inducing effects of tumor necrosis factor-alpha- through reactive oxygen species

The Journal of Toxicological Sciences
Pattama SinghirunnusornMathuros Ruchirawat

Abstract

Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine released by immune cells during inflammation process. Sodium arsenite (NaAsO2) is an environmental toxic metal. The effects of excess NaAsO2 on TNF-α response and its intracellular signaling are not well understood. We hypothesized that NaAsO2 exposure might affect cellular response to TNF-α. Using HeLa cell model, we found that the combination of NaAsO2 and TNF-α clearly decreased cell viability and mitochondrial membrane potential, but increased percentage of early and late apoptotic cells and cleaved-poly (ADP-ribose) polymerase (PARP). Moreover, the combination prolonged the phosphorylation of mitogen-activated protein kinase (MAPK) members, including c-Jun-N-terminal kinase (JNK), p38, and extracellular signal related kinases (ERK), and increased intracellular reactive oxygen species (ROS), in comparison to treatment of NaAsO2 or TNF-α alone. We further investigated the role of ROS and MAPK signaling on this event by inhibiting ROS production and MAPK. An antioxidant N-acetylcysteine pretreatment diminished the apoptosis-inducing effect of NaAsO2 and TNF-α combination and also inhibited MAPK signaling. Using specific inhibitor of p38 (SB203580) and siRNA-p38...Continue Reading

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Citations

Aug 18, 2020·BioMed Research International·Shanshan RanShugang Li

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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