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α‐Synuclein induced cell death in mouse hippocampal (HT22) cells is mediated by nitric oxide‐dependent activation of caspase‐3
Author(s) -
Adamczyk Agata,
Kaźmierczak Anna,
Czapski Grzegorz Arkadiusz,
Strosznajder Joanna Benigna
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.07.019
Subject(s) - poly adp ribose polymerase , nitric oxide , nitric oxide synthase , programmed cell death , extracellular , apoptosis , caspase 3 , chemistry , caspase , hippocampal formation , microbiology and biotechnology , biochemistry , biology , polymerase , enzyme , endocrinology , organic chemistry
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 Ca 2+ ‐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.