Evidence of Nrf2/Keap1 Signaling Regulation by Mitochodria-Generated Reactive Oxygen Species in RGK1 Cells
Hiroko P. Indo,
Daisuke Masuda,
Sompong Sriburee,
Hiromu Ito,
Ikuo Nakanishi,
Ken-ichiro Matsumoto,
Samlee Mankhetkorn,
Moragot Chatatikun,
Sirirat Surinkaew,
Lunla Udomwech,
Fumitaka Kawakami,
Takafumi Ichikawa,
Hirofumi Matsui,
Jitbanjong Tangpong,
Hideyuki J. Majima
Affiliations
Hiroko P. Indo
Department of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
Daisuke Masuda
Department of Space Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
Sompong Sriburee
Department of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
Hiromu Ito
Department of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
Ikuo Nakanishi
Quantum RedOx Chemistry Team, Institute for Quantum Life Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
Ken-ichiro Matsumoto
Quantitative RedOx Sensing Group, Department of Radiation Regulatory Science Research, National Institute of Radiological Sciences, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology (QST), Chiba 263-8555, Japan
Samlee Mankhetkorn
Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
Moragot Chatatikun
School of Allied Health Sciences, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand
Sirirat Surinkaew
School of Allied Health Sciences, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand
Lunla Udomwech
School of Medicine, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand
Fumitaka Kawakami
Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
Takafumi Ichikawa
Department of Regulation Biochemistry, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara 252-0373, Japan
Hirofumi Matsui
Division of Gastroenterology, Graduate School of Comprehensive Human Sciences, University Tsukuba, Tsukuba 305-8575, Japan
Jitbanjong Tangpong
School of Allied Health Sciences, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand
Hideyuki J. Majima
Department of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
It has been known that reactive oxygen species (ROS) are generated from the mitochondrial electron transport chain (ETC). Majima et al. proved that mitochondrial ROS (mtROS) caused apoptosis for the first time in 1998 (Majima et al. J Biol Chem, 1998). It is speculated that mtROS can move out of the mitochondria and initiate cellular signals in the nucleus. This paper aims to prove this phenomenon by assessing the change in the amount of manganese superoxide dismutase (MnSOD) by MnSOD transfection. Two cell lines of the same genetic background, of which generation of mtROS are different, i.e., the mtROS are more produced in RGK1, than in that of RGM1, were compared to analyze the cellular signals. The results of immunocytochemistry staining showed increase of Nrf2, Keap1, HO-1 and 2, MnSOD, GCL, GST, NQO1, GATA1, GATA3, GATA4, and GATA5 in RGK1 compared to those in RGM1. Transfection of human MnSOD in RGK1 cells showed a decrease of those signal proteins, suggesting mtROS play a role in cellular signals in nucleus.
