Alpha-synuclein induced cell death in mouse hippocampal (HT22) cells is mediated by nitric oxide-dependent activation of caspase-3

FEBS Letters
Agata AdamczykJoanna Benigna Strosznajder

Abstract

Our previous studies indicated that exogenous alpha-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 microM) 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 microM) 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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Citations

Jan 26, 2012·The Journal of Biological Chemistry·André ApostolatosNiketa A Patel
Jul 26, 2012·International Journal of Cell Biology·Rodney P Guttmann, Tamara J Powell
Feb 23, 2011·International Journal of Molecular Sciences·Elizabeth A MazzioKaram F A Soliman
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Apr 21, 2019·Journal of Neurochemistry·Amir Tayaranian MarvianTiago Fleming Outeiro
Nov 16, 2019·Cell Death & Disease·Goutham K GanjamCarsten Culmsee
Jun 4, 2020·International Journal of Molecular Sciences·Anna WilkaniecAgata Adamczyk
Feb 11, 2021·Antioxidants·Paulina BastianMagdalena Gorska-Ponikowska
Sep 28, 2020·Neurochemistry International·Henryk JęśkoAgata Adamczyk
Jul 3, 2021·International Journal of Molecular Sciences·Joanna A MotylRobert P Strosznajder

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