Alteration of sphingolipid biostat in experimental model of oxidative stress evoked by 1-methyl-4-phenylpyridinium (MPPplus)

• Autorzy: Pyszko J. , Strosznajder J. B.
• Języki publikacji: EN

Abstrakty

EN

Bioactive sphingolipids are important molecules that control wide spectrum of neuronal processes including neurotransmission, synaptic function, cells proliferation and death. Sphingosine kinases (SK1/2) are conserved enzymes that phosphorylate sphingosine to sphingosine-1-phosphate (S1P), which acts as a primary and secondary messenger. S1P binds to 5 receptors and plays essential role in neural signal transduction under physiological and various pathological conditions. Although growing evidence suggests important role of SK1/2 and S1P in neurodegenerative disorders including ischemia, inflammation and Alzheimer’s Disease, till now disturbances of sphingolipids homeostasis in Parkinson’s Disease (PD) remain unknown. Our study try to explain the role of SK1/2 and S1P in molecular mechanism of cell survival and death in model of oxidative stress evoked by neurotoxin 1-methyl-4-phenylpyridinium (MPP+), compound widely used in experimental model of PD. Our data presented that MPP+, comparable to SK inhibition evoked death of human neuroblastoma cells SH-SY5Y in time and concentration dependent manner. These changes are accompanied by increased free radicals concentration in these cells. Reduced level of SK1 protein was detected in SH-SY5Y cells after 24h exposure to MPP+ comparing to control. Moreover S1P pretreatment enhanced survival of these cells and protein level of SK1 comparing to MPP+ treated cells. Our data indicated that MPP+ evoked neuronal death is mediated by SK1/2 inhibition and altered sphingolipids signaling. These molecular events lead to caspase dependent apoptotic cells death and poly(ADP-ribose) polymerase-1 (PARP-1) degradation. All above results presented the alteration of sphingolipid biostat in experimental model of PD and suggested that S1P can offer novel, protective strategy.Supported by NCN Grant 5870/B/PO1/2011/40

Słowa kluczowe

EN

alteration; sphingolipid; experimental model; 1-methyl-4-phenylpyridinium; oxidative stress; neurotransmission; synaptic transmission; cell proliferation; sphingosine kinase 1; protective system

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

Twórcy

autor

Pyszko J.

• 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