Sphingosine kinase and glycogen synthase kinase-3Beta in molecular mechanism of Alzheimer’s amyloid Beta toxicity

• Autorzy: Czapski G.A. , Gassowska M. , Wilkaniec A. , Strosznajder J. B.
• Języki publikacji: EN

Abstrakty

EN

Alterations of phosphorylation-dephosphorylation processes play a crucial role in the pathomechanism of Alzheimer’s disease (AD). They affect signaling cascades and lead to hyperphosphorylation of tau protein. Glycogen synthase kinase 3β (Gsk-3β) is the main tau-kinase; however, little is known about the role of sphingolipid pathway in its regulation. Alteration of sphingolipid biostat may be an early event in etiopathology of AD. The question arises, if the sphingosine kinase (Sphk), a key enzyme in sphingolipid pathway, regulates Gsk-3β? We analyzed acute effects of exogenous amyloid β (Aβ) oligomers in PC12 cells, and prolonged exposition to endogenous Aβ in PC12 cells stably expressing human Swedish mutant APPsw gene. Our data indicated that in cells subjected to exogenous Aβ expression of Sphk1 and phosphorylation of Gsk-3β at Ser9 were enhanced, what could be considered as a component of protective mechanism. However, prolonged liberation of Aβ in APPsw cells evoked inhibition of Sphk1 expression, activation of Gsk-3β and death of significant population of cells. Consequently, an inhibitor of Sphk1 also reduced cell viability. Our data suggest the existence of specific relationship between Sphk1 and Gsk-3β and indicate their role in alteration of cell function and survival. The study was supported by MSHE Grant N401 587040.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: Suppl.1
• Opis fizyczny: p.52

Twórcy

autor

Czapski G.A.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Gassowska M.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Wilkaniec A.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Strosznajder J. B.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland