5'AMP-activated protein kinase α deficiency enhances stress-induced apoptosis in BHK and PC12 cells

Margaret M. Shaw (Lead / Corresponding author), Werner K. Gurr, Rory J. McCrimmon, Daniel F. Schorderet, Robert S. Sherwin

    Research output: Contribution to journalArticlepeer-review

    23 Citations (Scopus)

    Abstract

    5′AMP-activated protein kinase (AMPK) activation occurs under a variety of stress conditions but the role of this enzyme in the promotion or inhibition of stress-induced cell death is unclear. To address this issue, we transformed two different cell lines with shRNA-expressing plasmids, targeting the alpha subunit of AMPK, and verified AMPKα downregulation. The cell lines were then stressed by exposure to medium without glucose (PC12 cells) or with the viral thymidine kinase-specific DNA replication inhibitors: acyclovir, penciclovir and ganciclovir (herpes simplex virus thymidine kinase-expressing Baby Hamster Kidney cells). In non-AMPK-downregulated cells, these stress treatments induced AMPK upregulation and phosphorylation, leaving open the question whether the association of AMPK activation with stress-induced cell death reflects a successful death-promoting or an ineffective death-inhibiting activity. In AMPKα-deficient cells (expressing AMPKα-specific shRNAs or treated with Compound C) exposure to low glucose medium or DNA replication inhibitors led to an enhancement of cell death, indicating that, under the conditions examined, the role of activated AMPK is not to promote, but to protect from or delay stress-induced cell death.
    Original languageEnglish
    Pages (from-to)286-298
    Number of pages13
    JournalJournal of Cellular and Molecular Medicine
    Volume11
    Issue number2
    DOIs
    Publication statusPublished - Mar 2007

    Keywords

    • AMPK
    • AICAR
    • apoptosis
    • glucose
    • ACV
    • PCV
    • GCV

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