Mitochondrial-targeted active Akt protects SH-SY5Y neuroblastoma cells from staurosporine-induced apoptotic cell death

Paramita Mookherjee, Rodrigo Quintanilla, Myoung Sun Roh, Anna A. Zmijewska, Richard S. Jope, Gail V.W. Johnson

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Akt is a serine/threonine protein kinase that plays a vital role in promoting cellular survival. Predominantly cytosolic, upon stimulation with growth-factors or stress, active Akt translocates into mitochondria, but the functions of Akt in mitochondria are not yet fully understood. Mitochondria play a central role in apoptotic pathways and given Akt's functions in the cytoplasm, Akt in mitochondria may help preserve mitochondrial integrity during cellular stress. To test if the translocation of Akt into mitochondria is neuroprotective, adenoviral vectors expressing a constitutively active Akt, Ad-HA-Akt (DD), and a constitutively active Akt with a mitochondrial targeting signal, Ad-Mito-HA-Akt (DD), were generated. Human SH-SY5Y neuroblastoma cells expressing the adenoviral constructs were treated with staurosporine to initiate intrinsic apoptotic cell death and several aspects of the mitochondrial apoptotic pathway were evaluated. Expression of active Akt targeted to mitochondria was found to be sufficient to significantly reduce staurosporine-induced activation of caspase-3 and caspase-9, the release of cytochrome c from mitochondria, and Bax oligomerization at mitochondria. These findings demonstrate that intramitochondrial active Akt results in efficient protection against apoptotic signaling.

Original languageEnglish (US)
Pages (from-to)196-210
Number of pages15
JournalJournal of cellular biochemistry
Volume102
Issue number1
DOIs
StatePublished - Sep 1 2007

Keywords

  • Δψ
  • Akt
  • Apoptosis
  • Bax
  • Caspase
  • Mitochondria

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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