The regulation of Akt and FoxO transcription factors during dehydration in the African clawed frog ( Xenopus laevis )
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ORIGINAL PAPER
The regulation of Akt and FoxO transcription factors during dehydration in the African clawed frog (Xenopus laevis) Bryan E. Luu 1,2
&
Yichi Zhang 1,3
&
Kenneth B. Storey 1
Received: 17 February 2020 / Revised: 12 May 2020 / Accepted: 15 May 2020 # Cell Stress Society International 2020
Abstract The African clawed frog (Xenopus laevis) naturally tolerates severe dehydration using biochemical adaptation, one of which is the elevation of antioxidant defenses during whole-body dehydration. The present study investigated the role and regulation of a pathway known to regulate oxidative stress response, the Akt-FoxO signaling pathway, in clawed frog skeletal muscle, responding to medium (15%) and high (30%) dehydration. Protein levels of total and phosphorylated Akt, FoxO1, and FoxO3 were assessed via immunoblotting, in addition to the levels of the E3 ubiquitin ligase known to be associated with muscle atrophy, MAFbx. Akt activity/phosphorylation in addition to its total protein levels were decreased in the skeletal muscle during dehydration, and this corresponded with decreases in the relative phosphorylation of FoxO1 and FoxO3 as well on several residues. Akt is an inhibitor of FoxO1 and FoxO3 activity via phosphorylation, suggesting that FoxO activities were increased during dehydration stress. Furthermore, MAFbx showed decreased protein expression during high dehydration as well, suggesting that the clawed frog may exhibit some natural resistance to skeletal muscle atrophy during severe dehydration conditions. In addition to identifying that the suppression of Akt could lead to an activation of FoxO transcription factors in X. laevis during dehydration, these investigations suggest that X. laevis dehydration may implicate FoxO1 and FoxO3 in controlling skeletal muscle atrophy in X. laevis exposed to dehydration. This study implicates the Akt signaling pathway, its regulation of FoxO transcription factors, and FoxO-controlled targets, in stress adaptation against dehydration. Keywords Xenopus laevis . Akt . FoxO . Dehydration . Immunoblot
Introduction Many animals live in environments that can change to create conditions that can be stressful to the animal. Therefore, through evolution animals have developed various strategies to increase their chances of survival during periods of extreme environmental stress. The African clawed frog, Xenopus laevis, is a primarily aquatic frog that was described in 1803
* Kenneth B. Storey [email protected] 1
Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON K1S 5B6, Canada
2
Faculty of Medicine, McGill University, Montréal, Québec, Canada
3
Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
by Daudin. Wagler and Daudin both named the frog Xenopus for its peculiar clawed foot and laevi
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