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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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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DOI: https://doi.org/10.1007/s12017-007-8007-9