Activation of the 5'-AMP-Activated Protein Kinase in the Cerebral Cortex of Young Senescence-Accelerated P8 Mice and Association with GSK3β- and PP2A-Dependent Inhibition of p-tau₃₉₆ Expression.
Autor: | Kim, Hak-Su, Moon, Sohee, Paik, Jin-Hwe, Shin, Dong Wun, Kim, Lindsay S., Park, Chang-Shin, Ha, Joohun, Kang, Ju-Hee |
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Předmět: |
GENE expression
GENETICS of Alzheimer's disease PROTEIN kinases PROTEIN kinase genetics PHOSPHORYLATION AGING ANIMAL experimentation CELL differentiation CELL lines CEREBRAL cortex ESTERASES GENES GENETIC techniques HIPPOCAMPUS (Brain) MICE NERVE tissue proteins NEUROBLASTOMA PHOSPHOTRANSFERASES TRANSFERASES PHYSIOLOGY |
Zdroj: | Journal of Alzheimer's Disease; 2015, Vol. 46 Issue 1, p249-259, 11p |
Abstrakt: | The 5'-AMP-activated protein kinase (AMPK), which is a sensor of cellular energy, regulates neuronal survival and energy homeostasis. However, the roles of AMPK in the pathogenesis of Alzheimer's disease (AD) are unclear. The senescence-accelerated mouse prone 8 (SAMP8) strain is characterized by deficits in learning and memory, exhibits pathological characteristics of AD as early as 5 months of age, and is being increasingly recognized as a model of AD. Here, we investigated the relationship between AMPK activation and phosphorylation of the tau protein in the brain of young (2-month-old) SAMP8 animals and in differentiated SH-SY5Y cells. Upregulation of p-AMPK, p-ACC, and p-GSK3βS9 and downregulation of p-tau396 and sirtuin 1 (Sirt1) were observed in the cerebral cortex of young SAMP8 mice compared with that of age-matched SAMR1 animals. The hippocampal levels of p-AMPK and p-tau396 in SAMP8 animals were not significantly different from those of SAMR1, whereas upregulation of p-GSK3βS9 and downregulation of sirt1 was observed in the hippocampus of SAMP8 mice. Consistent with in vivo findings in the cortex, AMPK activation in SH-SY5Y cells upregulated p-GSK3βS9 but downregulated p-tau396, whereas it had no significant effect on p-tau262 expression. In addition, the AMPK-mediated inhibition of p-tau396 expression was attenuated by okadaic acid, a protein phosphatase 2A (PP2A) inhibitor. Taken together, our data showed that AMPK activation inhibits p-tau396 expression in a GSK3β- and PP2A-dependent manner, and suggest that differential regulation of tau phosphorylation in young SAMP8 mice by AMPK plays a compensatory role against accelerated senescence in this AD animal model. [ABSTRACT FROM AUTHOR] |
Databáze: | Complementary Index |
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