Aldehyde dehydrogenase 2*2 knock-in mice show increased reactive oxygen species production in response to cisplatin treatment

Journal of Biomedical Science
Jeewon KimDaria Mochly-Rosen

Abstract

The aldehyde dehydrogenase (ALDH) enzyme family metabolizes and detoxifies both exogenous and endogenous aldehydes. Since chemotherapeutic agents, such as cisplatin, generate cytotoxic aldehydes and oxidative stress, and chemoresistant cancer cells express high levels of ALDH enzymes, we hypothesized that different ALDH expression within cells may show different chemosensitivity. ALDH2 has the lowest Km for acetaldehyde among ALDH isozymes and detoxifies acetaldehydes in addition to other reactive aldehydes, such as 4-hydroxy-nonenal, malondialdehyde and acrolein produced from lipid peroxidation by reactive oxygen species (ROS). Thus, cells with an ALDH2 variant may sensitize them to these ROS-inducing chemotherapy drugs. Here, we used wild type C57BL/6 mice and ALDH2*2 knock-in mutant mice and compared the basal level of ROS in different tissues. Then, we treated the mice with cisplatin, isolated cells from organs and fractionated them into lysates containing mitochondrial and cytosolic fractions, treated with cisplatin again in vitro, and compared the level of ROS generated. We show that overall ROS production increases with cisplatin treatment in cells with ALDH2 mutation. The treatment of cisplatin in the wild type mice did...Continue Reading

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Citations

Feb 2, 2018·Nihon eiseigaku zasshi. Japanese journal of hygiene·Akiko Matsumoto
Dec 5, 2019·Environmental Science and Pollution Research International·Xiqian HuangChao Yuan
May 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shih-Hung TsaiYu-Juei Hsu
Feb 13, 2018·Expert Opinion on Therapeutic Targets·Thomas Münzel, Andreas Daiber
Dec 9, 2020·Seminars in Cancer Biology·Claudia PeitzschAnna Dubrovska

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