Evidence of Nrf2/Keap1 Signaling Regulation by Mitochondria-Generated Reactive Oxygen Species in RGK1 Cells

Indo, Hiroko P.; Masuda, Daisuke; Sriburee, Sompong; Ito, Hiromu; Nakanishi, Ikuo; Matsumoto, Ken‐ichiro; Mankhetkorn, Samlee; Chatatikun, Moragot; Surinkaew, Sirirat; Udomwech, Lunla; Kawakami, Fumitaka; Ichikawa, Takafumi; Matsui, Hirofumi; Tangpong, Jitbanjong; Majima, Hideyuki J.

doi:10.3390/biom13030445

Cited by 7 publications

(2 citation statements)

References 63 publications

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“…Majima et al were the first to report that reactive oxygen species (ROS) generated from the mitochondria promote apoptosis [106], while Itoh et al described the function of the Nrf2-Keap1 intercellular signal for the first time [107,108]. A recent study described that ROS generated from the mitochondria initiates cellular transduction in the cytosol [34,35]. The further roles of ROS and the subsequent intracellular signals, proteins, and molecule transport change need to be clarified.…”

Section: Discussionmentioning

confidence: 99%

“…The results showed that MnSOD transfected cells revealed a decrease in expression compared to those in the control. We previously demonstrated that mtROS causes intracellular signaling, and we published a paper entitled "Evidence of Nrf2/Keap1 Signaling Regulation by Mitochondrial-Generated Oxygen Species in RGK1 cells" in a Special Issue of Biomolecules entitled "The Physiological and Pathological New Function of Mitochondrial ROS and Intraorganellar Cross-Talks" in 2023 (https://www.mdpi.com/journal/biomolecules/special_issues/0XTJ2MAYET, accessed on 7 November 2023) [35]. They transfected MnSOD gene-contained vectors in a gastric mucosal tumorized cell line, RGK1 cells.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondria Play Essential Roles in Intracellular Protection against Oxidative Stress—Which Molecules among the ROS Generated in the Mitochondria Can Escape the Mitochondria and Contribute to Signal Activation in Cytosol?

Masuda,

Nakanishi,

Ohkubo

et al. 2024

Biomolecules

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Questions about which reactive oxygen species (ROS) or reactive nitrogen species (RNS) can escape from the mitochondria and activate signals must be addressed. In this study, two parameters, the calculated dipole moment (debye, D) and permeability coefficient (Pm) (cm s−1), are listed for hydrogen peroxide (H2O2), hydroxyl radical (•OH), superoxide (O2•−), hydroperoxyl radical (HO2•), nitric oxide (•NO), nitrogen dioxide (•NO2), peroxynitrite (ONOO−), and peroxynitrous acid (ONOOH) in comparison to those for water (H2O). O2•− is generated from the mitochondrial electron transport chain (ETC), and several other ROS and RNS can be generated subsequently. The candidates which pass through the mitochondrial membrane include ROS with a small number of dipoles, i.e., H2O2, HO2•, ONOOH, •OH, and •NO. The results show that the dipole moment of •NO2 is 0.35 D, indicating permeability; however, •NO2 can be eliminated quickly. The dipole moments of •OH (1.67 D) and ONOOH (1.77 D) indicate that they might be permeable. This study also suggests that the mitochondria play a central role in protecting against further oxidative stress in cells. The amounts, the long half-life, the diffusion distance, the Pm, the one-electron reduction potential, the pKa, and the rate constants for the reaction with ascorbate and glutathione are listed for various ROS/RNS, •OH, singlet oxygen (1O2), H2O2, O2•−, HO2•, •NO, •NO2, ONOO−, and ONOOH, and compared with those for H2O and oxygen (O2). Molecules with negative electrical charges cannot directly diffuse through the phospholipid bilayer of the mitochondrial membranes. Short-lived molecules, such as •OH, would be difficult to contribute to intracellular signaling. Finally, HO2• and ONOOH were selected as candidates for the ROS/RNS that pass through the mitochondrial membrane.

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