The role of sphingosine kinases/sphingosine-1-phosphate in the regulation of alpha-synuclein and amyloid beta precursor protein secretion. Implications for neurodegenerative disorders

• Autorzy: Jesko H. , Okada T. , Nakamura S. , Strosznajder R. P.
• Języki publikacji: EN

Abstrakty

EN

Sphingolipid deregulation may be an important factor of age-related neuronal stress vulnerability. Current data suggests potential links between sphingosine kinases (SphK1&2), their product sphingosine1-phosphate (S1P) and age-related protein conformation diseases. The aim of this study was to investigate a possible role of SphKs in alpha-synuclein (ASN) and amyloid beta (ABeta) precursor protein (APP) level and secretion. The studies were carried out using human SH-SY5Y neuroblastoma cell line stably transfected with the human gene for α-synuclein (ASNwt). Sphingosine kinase inhibitor (SKI) significantly increased ASN secretion in concentration-dependent manner. S1P also displayed similar influence. Neither compound exerted any significant effect on the ASN protein level. S1P may act via cell surface receptors or as an intracellular second messenger. The similar effect of S1P and SphK inhibitors on ASN secretion may suggest that the regulation of its release is critically dependent on the varied (intra)cellular targets of SphKs and downstream signaling pathways. We have found that stable human ASNwt expression in SH-SY5Y cells caused a three-fold, significant increase of the cellular APP level. In ASN-transfected cells S1P enhanced APP secretion and reduced its intracellular level. This could be linked to the recently reported effect of S1P on secretase beta activity. Inhibition of SphKs significantly decreased APP secretion. In summary our data indicates that endogenous ASN regulates APP level in SH-SY5Y cells and that sphingolipids play a crucial role in the secretion of ASN and APP. These processes may have significant impact on neuronal survival and health.

Słowa kluczowe

EN

sphingosine kinase 1; sphingosine 1-phosphate; sphingolipid; regulation; alpha-synuclein; amyloid beta precursor; protein secretion; neurodegenerative disorder; neuronal stress; vulnerability; human disease; age-related disease

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.175-176

Twórcy

autor

Jesko H.

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

autor

Okada T.

• Division of Biochemistry, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan

autor

Nakamura S.

• Division of Biochemistry, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan

autor

Strosznajder R. P.

• Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland