Original Paper

NeuroMolecular Medicine

, Volume 9, Issue 3, pp 255-263

Differential Regulation of Smac/DIABLO and Hsp-70 during Brain Maturation

  • Veronika StokaAffiliated withBuck Institute for Age ResearchDepartment of Biochemistry, Molecular and Structural Biology, J. Stefan Institute
  • , Vito TurkAffiliated withDepartment of Biochemistry, Molecular and Structural Biology, J. Stefan Institute
  • , Dale E. BredesenAffiliated withBuck Institute for Age ResearchDepartment of Neurology, University of California Email author 

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Abstract

The heat shock protein (Hsp) system is a cell defense mechanism constitutively expressed at the basal state and essential for cell survival in response to damaging stimuli. Apoptosis is a physiological cell death program that preserves tissue homeostasis. We investigated the intrinsic pathway of apoptosis at various stages of brain maturation in CD-1 mice, triggered by two mitochondrial proapoptotic proteins, cytochrome c and Smac/DIABLO, and the pathway’s regulation by Hsp-70. Smac/DIABLO and Hsp-70 proteins were upregulated 2-fold and 1.5–3-fold, respectively, after birth. In contrast, in the presence of cytochrome c/2′-deoxyadenosine 5′-triphosphate (dATP), caspase activity in mouse brain cell-free extracts increased 90-fold and 61-fold, at fetal and neonatal stages, whereas no activation was detected 15 days postnatally or at any subsequent times. These results indicate that the activation pattern of the intrinsic pathway of apoptosis undergoes a marked shift during postnatal maturation.

Keywords

Aging Apoptosis Brain maturation Caspase activation Cytochrome c-mediated apoptosis Development Hsp-70 regulation Intrinsic pathway Neuronal cell death Smac/DIABLO regulation