TitleAge-associated impairment of Akt phosphorylation in primary rat hepatocytes is remediated by alpha-lipoic acid through PI3 kinase, PTEN, and PP2A.
Publication TypeJournal Article
Year of Publication2009
AuthorsShay KPetersen, Hagen TM
Date Published2009 Aug
KeywordsAge Factors, Aging, Animals, Antioxidants, Cell Survival, Cells, Cultured, Hepatocytes, Insulin, Male, Oxidative Stress, Phosphatidylinositol 3-Kinases, Phosphorylation, Protein Phosphatase 2, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Rats, Rats, Inbred F344, Serine, Signal Transduction, Thioctic Acid

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)-alpha-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 microM) 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.

Alternate JournalBiogerontology
PubMed ID18931933
PubMed Central IDPMC2700853
Grant ListR01 AG017141 / AG / NIA NIH HHS / United States
T32 AT002688-01 / AT / NCCIH NIH HHS / United States
R01 2AG17141 / AG / NIA NIH HHS / United States
P01 AT002034-010002 / AT / NCCIH NIH HHS / United States
T32 AT002688 / AT / NCCIH NIH HHS / United States
R01 AG017141-01A1 / AG / NIA NIH HHS / United States
P01 AT002034 / AT / NCCIH NIH HHS / United States
P01 AT002034-01 / AT / NCCIH NIH HHS / United States