Decrease of Tau hyperphosphorylation by 17β estradiol requires sphingosine kinase in a glutamate toxicity model.
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 17β-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 17β-estradiol requires SphK.
Lopez-Tobón
Alejandro
A
Group of Neuroscience of Antioquia, Cellular and Molecular Neurobiology Area, School of Medicine, SIU, University of Antioquia, Street 62 # 52-59; Tower 1, Floor 4th, Laboratory 411-412, Medellín, Colombia.
Cepeda-Prado
Efraín
E
Cardona-Gómez
Gloria Patricia
GP
D000199:Actins / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*; D000099157:Sphingosine Kinase
D000199:Actins; D004958:Estradiol; D018698:Glutamic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D051057:Proto-Oncogene Proteins c-akt; D016875:tau Proteins; D000099157:Sphingosine Kinase