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Mitochondrial ROS induced by ML385, an Nrf2 inhibitor aggravates the ferroptosis induced by RSL3 in human lung epithelial BEAS-2B cells.

Authors :
Taufani, Indra Putra
Situmorang, Jiro Hasegawa
Febriansah, Rifki
Tasminatun, Sri
Sunarno, Sunarno
Yang, Liang-Yo
Chiang, Yi-Ting
Huang, Chih-Yang
Source :
Human & Experimental Toxicology; Jan-Dec2023, Vol. 42, p1-10, 10p
Publication Year :
2023

Abstract

Ferroptosis is a new type of cell death marked by iron and lipid ROS accumulation. GPX4 is one of the glutathione peroxidases known to regulate ferroptosis tightly. On the other hand, Nrf2 also plays a vital role in ferroptosis as it targets genes related to oxidant defense. Herein, we employed beas-2 human epithelial cells treated with a low concentration of RSL3 to induce ferroptosis. To study the protective role of Nrf2, we used ML385 as its specific inhibitor. A combination of ML385 and a low concentration of RSL3 synergistically induced more toxicity to RSL3. Furthermore, we found that mitochondrial ROS is elevated in ML385 and RSL3 combination group. In addition, Mito TEMPOL application successfully prevents the upregulation of mitochondrial ROS, lipid ROS, reduces the toxicity of RSL3, restores the antioxidant capacity of the cells, and mitochondrial functions reflected by mitochondrial membrane potential and mitochondrial oxidative phosphorylation system (OXPHOS) expression. Altogether, our study demonstrated that Nrf2 inhibition by ML385 induces more toxicity when combined with RSL3 through the elevation of mitochondrial ROS and disruption of mitochondrial function. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09603271
Volume :
42
Database :
Complementary Index
Journal :
Human & Experimental Toxicology
Publication Type :
Academic Journal
Accession number :
175197526
Full Text :
https://doi.org/10.1177/09603271221149663