Decrease of Tau Hyperphosphorylation by 17 beta Estradiol Requires Sphingosine Kinase in a Glutamate Toxicity Model

作者：Lopez Tobon Alejandro; Cepeda Prado Efrain; Patricia Cardona Gomez Gloria

来源：Neurochemical Research, 2009, 34(12): 2206-2214.

DOI：10.1007/s11064-009-0017-6

• Neuroprotection
• 17 beta-Estradiol
• Glutamate
• Sphingosine kinase 1 (Sphk-1)
• Hyperphosphorylated tau

Several studies have linked estrogens with sphingosine kinase (SphK) activity, enzyme responsible of sphingosine-1-phosphate synthesis (S-1P), however their possible interaction in the nervous system is not documented yet. In the present study, we developed a glutamate toxicity model in SH-SY5Y cells to evaluate the possible effect of the inhibition of SphK activity on the protective capability of 17 beta-estradiol (E2). Glutamate induced cytoskeletal actin changes associated to cytotoxic stress, significant increase of apoptotic-like nuclear fragmentation, Tau hyperphosphorylation and increase of p25/p35 cleavage. These effects were prevented by E2 pre-treatment during 24 h. Although the inhibition of SphK did not block this protective effect, significantly increased Tau hyperphosphorylation by glutamate, in a way that was not reverted by E2. Our results suggest that the decrease of glutamate-induced Tau hyperphosphorylation by 17 beta-estradiol requires SphK.

• 出版日期2009-12