The Thioredoxin System of Mammalian Cells and Its Modulators

Biomedicines - Tập 10 Số 7 - Trang 1757
Aseel Ali Hasan1, Elena Kalinina1, Victor V. Tatarskiy2, Аlexander А. Shtil3
1T.T. Berezov Department of Biochemistry, Peoples' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia
2Laboratory of Molecular Oncobiology, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov Street, 119334 Moscow, Russia
3Laboratory of Tumor Cell Death, Blokhin National Medical Research Center of Oncology, 24 Kashirskoye Shosse, 115478 Moscow, Russia

Tóm tắt

Oxidative stress involves the increased production and accumulation of free radicals, peroxides, and other metabolites that are collectively termed reactive oxygen species (ROS), which are produced as by-products of aerobic respiration. ROS play a significant role in cell homeostasis through redox signaling and are capable of eliciting damage to macromolecules. Multiple antioxidant defense systems have evolved to prevent dangerous ROS accumulation in the body, with the glutathione and thioredoxin/thioredoxin reductase (Trx/TrxR) systems being the most important. The Trx/TrxR system has been used as a target to treat cancer through the thiol–disulfide exchange reaction mechanism that results in the reduction of a wide range of target proteins and the generation of oxidized Trx. The TrxR maintains reduced Trx levels using NADPH as a co-substrate; therefore, the system efficiently maintains cell homeostasis. Being a master regulator of oxidation–reduction processes, the Trx-dependent system is associated with cell proliferation and survival. Herein, we review the structure and catalytic properties of the Trx/TrxR system, its role in cellular signaling in connection with other redox systems, and the factors that modulate the Trx system.

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