Suppression of protein kinase Cε mediates 17β-estradiol-induced neuroprotection in an immortalized hippocampal cell line

Marianna E. Jung, David G. Watson, James W. Simpkins

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7 Scopus citations


Although estrogens are neuroprotective in a variety of neuroprotection models, the precise underlying mechanisms are currently not well understood. Here, we examined the role of protein kinase C (PKC) in mediating estrogen-induced neuroprotection in the HT-22 immortalized hippocampal cell line. The neuroprotection model utilized calcein fluorescence to quantitate cell viability following glutamate insults. 17β-Estradiol (βE2) protected HT-22 cells when treatment was initiated before or after the glutamate insult. The inhibition of PKC by bis-indolylmaleimide mimicked and enhanced βE2-induced neuroprotection. In contrast, the inhibition of specific PKC isozymes (α and β) by Go6976, inhibition of 1-phosphatidylinositol 3 kinase by wortmannin, or inhibition of protein kinase A by H-89, did not alter cell viability, suggesting a specific involvement of PKC in an isozyme-dependent manner. We further examined whether estrogen interacts with PKC in a PKC isozyme-specific manner. Protein levels and activity of PKC isozymes (α, δ, ε, and ζ) were assessed by western blot analysis and radiolabeled phosphorylation assays respectively. Among the isozymes tested, βE2 altered only PKCε; it reduced the activity and membrane translocation of PKCε in a manner that correlated with its protection against glutamate toxicity. Furthermore, βE2 reversed the increased activity of membrane PKCε induced by glutamate. These data suggest that the neuroprotective effects of estrogens are mediated in part by inhibition of PKCε activity and membrane translocation.

Original languageEnglish
Pages (from-to)745-755
Number of pages11
JournalJournal of Neurochemistry
Issue number3
StatePublished - 2005


  • 17β-estradiol
  • Estrogens
  • Hippocampal cells
  • Neuroprotection
  • Protein kinase C inhibitors
  • Protein kinase Cε


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