Differential regulation of phosphatidylinositol 3-kinase/Akt, mitogen-activated protein kinase, and AMP-activated protein kinase pathways during menadione-induced oxidative stress in the kidney of young and old rats

Quanri Jin, Bong Sook Jhun, Suk Hyoung Lee, Jinhwa Lee, Yonghao Pi, Yong Ho Cho, Hyung Hwan Baik, Insug Kang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

We investigated regulation of various signal transduction pathways during oxidative stresses in the kidney of young and aged rats. Menadione-induced regulation of molecules in PI 3-kinase, MAPK, and AMPK pathways was determined in the young (2 months) and old (24 months) groups. PI 3-kinase activity and Akt phosphorylation were significantly reduced in the old compared with the young. PTEN tumor suppressor was also lower in its expression and phosphorylation levels in the old. Response of the molecules in PI 3-kinase pathway to menadione was minimized. In contrast, over 5-fold induction of ERK1/ 2 phosphorylation by menadione was observed in both groups. On the other hand, basal activities as well as menadione-induced activities of JNK1 and AMPK were higher in the old than in the young. While p27Kip1, p53, and p21 Waf1 were slightly increased by menadione in both groups, the basal induction level in the old was considerably higher. In conclusion, the results suggest that the age-related down-regulation of PI 3-kinase/Akt pathway and up-regulation of JNK1, AMPK, and p53 pathways may be responsible for the increased susceptibility to oxidative stress.

Original languageEnglish (US)
Pages (from-to)555-561
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume315
Issue number3
DOIs
StatePublished - Mar 12 2004
Externally publishedYes

Keywords

  • AMPK
  • Aging
  • Apoptosis
  • MAPK
  • Menadione
  • PI 3-kinase
  • PTEN
  • Rat kidney
  • Reactive oxygen species
  • p53

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