Ceramides and sphingosine-1-phosphate in molecular mechanisms of neuronal cell death

• Autorzy: Czubowicz K. , Strosznajder R. P.
• Języki publikacji: EN

Abstrakty

EN

Ceramides, bioactive members of the sphingolipids can be generated by de novo synthesis, sphingomyelin hydrolysis and by acylation of sphingosine. Ceramides are known to regulate several cellular processes, including differentiation, growth suppression, cell senescence and apoptosis. The ceramide levels increased in several pathological conditions such as brain ischemia, hypoglycemia, inflammation and in neurodegenerative disorders. Sphingosine, a metabolite of ceramide is phosphorylated by sphingosine kinases (Sphk type 1and 2) to sphingosine-1-phosphate (S1P). Sphingosine kinases are critical regulators of the sphingolipid biostat. The aim of this study was to investigate the role of ceramide and S1P in molecular mechanisms of neuronal cells death. The human neuroblastoma cell line (SH-SY5Y) was exposed to cell-permeable C2-ceramide. Ceramide decreased the viability of SH-SY5Y cells in concentration dependent manner. The intracellular free radical generation after ceramide treatment was about 3-fold higher comparing to control. Concomitantly our study indicated that ceramide induced poly(ADP-ribose) polymerase-1 (PARP-1) activation and decreased the level of apoptosis inducing factor (AIF) in mitochondria. Ceramide diminished the expression and level of anti-apoptotic Bcl-2 protein. PARP-1 inhibitor enhanced the level of Bcl-2 protein and cells survival keeping the level of AIF in mitochondria unchanged. The recent studies indicated that ERK1/2 are involved directly in regulation of PARP-1 activity. The specific inhibitor of these kinases protected cells against death evoked by ceramide in our experimental conditions. Moreover, our study indicated, that sphingosine-1-phosphate (S1P) increased Bcl-2 gene expression and SH-SY5Y cells survival after ceramide treatment. Summarizing, our data present that PARP-1 inhibitor and sphingosine-1-phosphate (S1P) through modulation of anti-apoptotic proteins protect mitochondria and neuronal cells against death evoked by ceramide. Supported by statutory budget of MRC and NCN Grant 5870/PO1/2011/40

Słowa kluczowe

EN

ceramide; sphingosine 1-phosphate; molecular mechanism; neuronal cell; apoptosis; cellular process; pathological condition

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.194

Twórcy

autor

Czubowicz K.

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

autor

Strosznajder R. P.

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