α-Synuclein induced cell death in mouse hippocampal (HT22) cells is mediated by nitric oxide-dependent activation of caspase-3 |
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Authors: | Agata Adamczyk Anna Ka?mierczak Grzegorz Arkadiusz Czapski Joanna Benigna Strosznajder |
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Institution: | Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland |
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Abstract: | Our previous studies indicated that exogenous α-synuclein (ASN) activates neuronal nitric oxide (NO) synthase (nNOS) in rat brain slices. The present study, carried out on immortalized hippocampal neuronal cells (HT22), was designed to extend the previous results by showing the molecular pathway of NO-mediated cell death induced by exogenous ASN. Extracellular ASN (10 μM) was found to stimulate nitric oxide synthase (NOS) and increase caspase-3 activity in HT22 cells, leading to poly(ADP-ribose) polymerase (PARP-1) cleavage. The inhibitor of Ca2+-dependent NOS (N-nitro-l-arginine, 100 μM) prevented ASN-evoked caspase-3 activation and PARP-1 degradation. ASN exposure resulted in apoptotic death of HT22 cells and this effect was reversed by inhibition of NO synthesis and caspase-3 activity. Our results demonstrated that extracellular ASN induces neuronal cell death by NO-mediated caspase-3 activation. |
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Keywords: | α-Synuclein Nitric oxide Caspase-3 Poly(ADP-ribose) polymerase-1 HT22 cell |
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