Estradiol attenuates tau hyperphosphorylation induced by upregulation of protein kinase-A.
Protein kinase A (PKA) plays a crucial role in tau hyperphosphorylation, an early event of Alzheimer disease (AD), and 17beta-estradiol replacement in aging women forestalls the onset of AD. However, the role of estradiol in PKA-induced tau hyperphosphorylation is not known. Here, we investigated the effect of 17beta-estradiol on cAMP/PKA activity and the PKA-induced tau hyperphosphorylation in HEK293 cells stably expressing tau441. We found that 17beta-estradiol effectively attenuated forskolin-induced overactivation of PKA and elevation of cAMP, and thus prevented tau from hyperphosphorylation. These data provide the first evidence that 17beta-estradiol can inhibit PKA overactivation and the PKA-induced tau hyperphosphorylation, implying a preventive role of 17beta-estradiol in AD-like tau pathology.
Liu
Xin-An
XA
Pathophysiology Department, Tongji Medical College, Hua-Zhong University of Science and Technology, Wuhan, 430030, PR China.
Zhu
Ling-Qiang
LQ
Zhang
Qi
Q
Shi
Hai-Rong
HR
Wang
Shao-Hui
SH
Wang
Qun
Q
Wang
Jian-Zhi
JZ
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D016875:tau Proteins / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D016875:tau Proteins; D005576:Colforsin; D004958:Estradiol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases