We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Arsenite exposure potentiates apoptosis-inducing effects of tumor necrosis factor-alpha- through reactive oxygen species.
- Authors
Pattama Singhirunnusorn; Benchamart Moolmuang; Kriengsak Lirdprapamongkol; Mathuros 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 excessNaAsO2on TNF-αresponse 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 ofNaAsO2and TNF-αclearly 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 mitogenactivated 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 ofNaAsO2or TNF-αalone. 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 ofNaAsO2and TNF-αcombination and also inhibited MAPK signaling. Using specific inhibitor of p38 (SB203580) and siRNA-p38 surprisingly increased cell apoptosis and this effect was not observed by JNK and ERK inhibition. This study suggests that p38 may possibly be a survival mediator in response to environmental toxicant-related inflammation. In conclusion, NaAsO2 exposure might amplify inflammation-related tissue injury by potentiating the apoptosisinducing effect of TNF-αthrough ROS-dependent mechanism.
- Subjects
SODIUM arsenite; TUMOR necrosis factors; APOPTOSIS; MITOGEN-activated protein kinases; REACTIVE oxygen species
- Publication
Journal of Toxicological Sciences, 2018, Vol 43, Issue 2, p159
- ISSN
0388-1350
- Publication type
Article