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

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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.

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Acknowledgments

The authors are thankful to Sylvia F. Chen for technical assistance during brain tissue preparation. This study was supported by NIH grants AG12282 and NS33376 to D.E.B. and grant P1-0140 from the Ministry of Higher Education, Science and Technology of the Republic of Slovenia to V.T.

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Authors and Affiliations

  1. Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA, 94945, USA

    Veronika Stoka & Dale E. Bredesen

  2. Department of Biochemistry, Molecular and Structural Biology, J. Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia

    Veronika Stoka & Vito Turk

  3. Department of Neurology, University of California, San Francisco, CA, 94143, USA

    Dale E. Bredesen

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  1. Veronika Stoka
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  2. Vito Turk
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Correspondence to Dale E. Bredesen.

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Vito Turk and Dale E. Bredesen share senior authorship.

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Stoka, V., Turk, V. & Bredesen, D.E. Differential Regulation of Smac/DIABLO and Hsp-70 during Brain Maturation. Neuromol Med 9, 255–263 (2007). https://doi.org/10.1007/s12017-007-8007-9

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