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Age-associated impairment of Akt phosphorylation in primary rat hepatocytes is remediated by alpha-lipoic acid through PI3 kinase, PTEN, and PP2A

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Abstract

Akt is a highly regulated serine/threonine kinase involved in stress response and cell survival. Stress response pathways must cope with increasing chronic stress susceptibility with age. We found an age-related lesion in Akt activity via loss of phosphorylation on Ser473. In hepatocytes from old rats, basal phospho-Ser473 Akt is 30% lower when compared to young, but basal phospho-Thr308 Akt is unchanged. (R)-α-lipoic acid (LA), a dithiol compound with antioxidant properties, is effective against age-related increases in oxidative stress and has been used to improve glucose utilization through insulin receptor (IR) pathway-mediated Akt phosphorylation. Treatment with physiologically relevant doses of LA (50 μM) provided a 30% increase in phospho-Ser473. Furthermore, two phosphatases that antagonize Akt, PTEN and PP2A, were both partially inhibited by LA. Thus, LA may be a nutritive agent that can remediate loss of function in the Akt pathway and aid in the survival of liver cells.

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Acknowledgments

This work was supported by grants from the National Institutes of Health R01 2AG17141 and P01 AT002034-01. KPS was supported by T32 AT002688-01.

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Authors and Affiliations

  1. Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR, 97331-6512, USA

    Kate Petersen Shay & Tory M. Hagen

  2. Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, 97331, USA

    Tory M. Hagen

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  1. Kate Petersen Shay
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  2. Tory M. Hagen
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Correspondence to Tory M. Hagen.

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Petersen Shay, K., Hagen, T.M. Age-associated impairment of Akt phosphorylation in primary rat hepatocytes is remediated by alpha-lipoic acid through PI3 kinase, PTEN, and PP2A. Biogerontology 10, 443–456 (2009). https://doi.org/10.1007/s10522-008-9187-x

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  • DOI: https://doi.org/10.1007/s10522-008-9187-x

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