Differential thiol oxidation of the signaling proteins Akt,PTEN or PP2A determines whether Akt phosphorylation is enhanced or inhibited by oxidative stress in C2C12 myotubes derived from skeletal muscle |
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| Institution: | 1. School of Anatomy, Physiology and Human Biology, The University of Western Australia, Western Australia, Australia;2. School of Chemistry and Biochemistry, The University of Western Australia, Western Australia, Australia;1. College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China;2. Sichuan Province General Station of Animal Husbandry, Chengdu 611130, China;3. College of Life and Science, Sichuan Agricultural University, Chengdu 611130, China;4. Chongqing Academy of Animal Sciences, Chongqing 402460, China;1. Department of Neurology, Affiliated Dalian Central Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China;2. Central Laboratory, Affiliated Dalian Central Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China;3. Department of Histology and Embryology, Colleges of Basic Medical Sciences, Dalian Medical University, Dalian 116044, Liaoning Province, China;1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada;2. Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan;3. Department of Biochemistry, Faculty of Life Sciences, University of Central Punjab, Lahore 54590, Pakistan;4. Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia 7003, Bangladesh;5. Department of Biochemistry and Molecular Biology, University of Calgary, T2N 1N4 Alberta, Canada;6. Department of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyunghee dae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea;1. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA;2. Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX, USA;1. Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea;2. Department of Functional Genomics, Korea University of Science and Technology, Daejeon 305-333, Republic of Korea;3. Well Aging Research Center, Samsung Advanced Institute of Technology, Samsung Electronics Co. Ltd, Gyeonggi-do 446-712, Republic of Korea;4. Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea;5. Graduate School of Pharmaceutical Sciences, Ewha Women?s University, Seoul 120-750, Republic of Korea |
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| Abstract: | Oxidative stress, caused by excess reactive oxygen species (ROS), has been hypothesized to cause or exacerbate skeletal muscle wasting in a number of diseases and chronic conditions. ROS, such as hydrogen peroxide, have the potential to affect signal transduction pathways such as the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3 K)/Akt pathway that regulates protein synthesis. Previous studies have found contradictory outcomes for the effect of ROS on the PI3K/Akt signaling pathway, where oxidative stress can either enhance or inhibit Akt phosphorylation. The apparent contradictions could reflect differences in experimental cell types or types of ROS treatments. We replicate both effects in myotubes of cultured skeletal muscle C2C12 cells, and show that increased oxidative stress can either inhibit or enhance Akt phosphorylation. This differential response could be explained: thiol oxidation of Akt, but not the phosphatases PTEN or PP2A, caused a decline in Akt phosphorylation; whereas the thiol oxidation of Akt, PTEN and PP2A increased Akt phosphorylation. These observations indicate that a more complete understanding of the effects of oxidative stress on a signal transduction pathway comes not only from identifying the proteins susceptible to thiol oxidation, but also their relative sensitivity to ROS. |
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| Keywords: | Oxidative stress Reactive oxygen species Hydrogen peroxide Protein thiol oxidation Akt |
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