TXNIP regulates AKT-mediated cellular senescence by direct interaction under glucose-mediated metabolic stress

Aging Cell
Hangsak HuyInpyo Choi

Abstract

Aging is associated with an inevitable and universal loss of cell homeostasis and restricts an organism's lifespan by an increased susceptibility to diseases and tissue degeneration. The glucose uptake associated with producing energy for cell survival is one of the major causes of ROS production under physiological conditions. However, the overall mechanisms by which glucose uptake results in cellular senescence remain mysterious. In this study, we found that TXNIP deficiency accelerated the senescent phenotypes of MEF cells under high glucose condition. TXNIP-/- MEF cells showed greater induced glucose uptake and ROS levels than wild-type cells, and N-acetylcysteine (NAC) treatment rescued the cellular senescence of TXNIP-/- MEF cells. Interestingly, TXNIP-/- MEF cells showed continuous activation of AKT during long-term subculture, and AKT signaling inhibition completely blocked the cellular senescence of TXNIP-/- MEF cells. In addition, we found that TXNIP interacted with AKT via the PH domain of AKT, and their interaction was increased by high glucose or H2 O2 treatment. The inhibition of AKT activity by TXNIP was confirmed using western blotting and an in vitro kinase assay. TXNIP deficiency in type 1 diabetes mice (Akita...Continue Reading

References

Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·L YaoT Kawakami
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P DimriO Pereira-Smith
Aug 29, 1997·The Journal of Biological Chemistry·L E RamehL C Cantley
Mar 21, 2001·FEBS Letters·E HajduchH S Hundal
Feb 23, 2005·Immunity·Kee Nyung LeeInpyo Choi
May 4, 2005·Molecular Cell·Russell G JonesCraig B Thompson
May 3, 2007·PLoS Medicine·Hemang ParikhVamsi K Mootha
Nov 14, 2007·The Journal of Biological Chemistry·William A ChutkowRichard T Lee
Mar 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Simon T Y HuiRoger A Davis
Sep 16, 2008·Molecular Cancer Therapeutics·Daruka MahadevanEmmanuelle J Meuillet
Dec 9, 2008·Cancer Cell·Ignacio Dolado, Angel R Nebreda
Aug 14, 2010·Journal of the American Society of Nephrology : JASN·Haichun Yang, Agnes B Fogo
Sep 8, 2010·The Biochemical Journal·Shi-Xiong TanDavid E James
Nov 17, 2010·Genes & Development·Thomas KuilmanDaniel S Peeper
Feb 23, 2012·Scientific Reports·Riekelt H HoutkooperJohan Auwerx
Nov 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Chaitali ParikhSomasekar Seshagiri
Jan 18, 2013·Nature·Simon C JohnsonMatt Kaeberlein
Apr 2, 2014·Current Opinion in Hematology·Haiyoung Jung, Inpyo Choi
Jan 1, 2015·ELife·Igor VivancoIngo K Mellinghoff

❮ Previous
Next ❯

Citations

Jan 4, 2020·Cellular and Molecular Life Sciences : CMLS·Janusz Blasiak
Jan 15, 2020·American Journal of Physiology. Endocrinology and Metabolism·XiaoLong JiangHuaBin Zhu
Sep 12, 2019·Pharmaceuticals·Angie C Romero-AriasLudis Morales
Aug 23, 2020·Antioxidants·Eiji Yoshihara
Dec 18, 2020·International Journal of Molecular Sciences·Dong Oh KimHaiyoung Jung
Feb 10, 2021·Chemical Biology & Drug Design·Li ZhongMing-Wei Wang
May 25, 2021·Neurobiology of Disease·Saifudeen IsmaelTauheed Ishrat
Jun 10, 2021·Laboratory Investigation; a Journal of Technical Methods and Pathology·Qian-Qian ZhuHong-Kun Zhang
Jun 3, 2021·Npj Aging and Mechanisms of Disease·Nicholas HolzscheckLars Kaderali

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
flow cytometry
immunoprecipitation
proximity ligation assay
proximity ligation

Software Mentioned

CS Analyzer
Prism

Related Concepts

Related Feeds

Cell Aging

This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.