Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1830, Issue 10, Pages 4828-4837Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2013.06.020
Keywords
Freeze tolerance; miRNA; FOXO1; PDK-1; PTEN; Apoptosis
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Funding
- Natural Sciences and Engineering Research Council (NSERC) of Canada
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Background: The wood frog (Rana sylvatica) exhibits well-developed natural freeze tolerance supported by multiple mechanisms of biochemical adaptation. The present study investigated the role and regulation of the Akt signaling pathway in wood frog tissues (with a focus on liver) responding to freezing stress. Methods: Immunoblotting was used to assess total and phospho-Akt levels, total and phospho-PDK1, PTEN protein level, as well as total and phospho-FOXO1 levels. RT-PCR was used to investigate transcript levels of PTEN and microRNAs. Results: Akt was inhibited in skeletal muscle, kidney and heart after 24 h freezing exposure with a reversal after thawing. The responses of the main kinase (PDK-1) and phosphatase (PTEN) that regulate Akt were consistent with freeze activation of Akt in liver; freezing exposure activated PDK-1 via enhanced Ser-241 phosphorylation whereas PTEN protein levels were reduced. Levels of three microRNAs (miR-26a, miR-126 and miR-217) that regulate pten expression were elevated in liver during freezing. One well-known role of Akt is in anti-apoptosis, mediated in part by Akt phosphorylation of Ser-256 on FOXO1. Freezing triggered an increase in liver phospho-FOXO1 Ser-256 content, suggesting that an important action of Akt may be apoptosis inhibition. Conclusions: Akt activation in wood frog is stress and tissue specific, with multi-facet regulations (posttranslatonal and posttranscriptional) involved in supporting this specific signal transduction response. General significance: This study implicates the Akt pathway in the metabolic reorganization of cellular metabolism in support of freezing survival. (c) 2013 Elsevier B.V. All rights reserved.
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