title: Human tau may modify glucocorticoids-mediated regulation of cAMP-dependent kinase and phosphorylated cAMP response element binding protein.
abstract: Phosphorylation of the cAMP response element binding protein (CREB) by cAMP-dependent kinase (PKA) is critical to memory formation. However, activation of PKA can also increase tau phosphorylation, which may contribute to memory impairment. Therefore, the regulation of PKA may be part of the mechanism by which glucocorticoids (GCs) influence memory. Additionally, the cellular response to GCs may be affected by the presence of human tau. The goal of this paper was to study GCs-mediated regulation of PKA as well as CREB and tau phosphorylation in wild-type HEK293 cells and HEK293 cells stably expressing human tau441 (HEK293/tau441 cells). By using dexamethasone (DEX) as GCs, we found that DEX induced a tau-dependent selective decrease in the level of PKA RIIβ subunit protein. The observed decrease in RIIβ expression was not due to alterations of mRNA levels and was reversed by inhibiting the proteasome with lactacystin. Moreover, the decrease in RIIβ did not diminish the co-localization of the catalytic subunit of PKA with tau and might contribute to the DEX-induced increase in tau phosphorylation at Ser-214. DEX also induced a tau-dependent decrease in CREB phosphorylation that could not be reversed by activating PKA with forskolin. Taken together, these results show that human tau protein may alter the GCs-mediated regulation of PKA activity and CREB phosphorylation.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Su
authors.forename: Shenggang
authors.initials: S
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Xian
authors.initials: X
authors.lastname: Qiao
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Run
authors.forename: Zhihou
authors.initials: Z
authors.lastname: Liang
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D010766:Phosphorylation; D061988:Proteasome Inhibitors; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D061988:Proteasome Inhibitors; D016875:tau Proteins; D005576:Colforsin; D003907:Dexamethasone; D017868:Cyclic AMP-Dependent Protein Kinases