Neuroprotective Effects of Neuropeptide Y on Human Neuroblastoma SH-SY5Y Cells in Glutamate Excitotoxicity and ER Stress Conditions
Authors:
- Viswanthram PalanivelVPViswanthram Palanivel
- Vivek GuptaVivek Gupta
- Seyed Shahab Oddin MirshahvaladiSMSeyed Shahab Oddin Mirshahvaladi
- Samridhi SharmaSSSamridhi Sharma
- Veer GuptaVGVeer Gupta
- Nitin ChitranshiNCNitin Chitranshi
- Mehdi MirzaeiMMMehdi Mirzaei
- Stuart L GrahamSGStuart L Graham
- Devaraj BasavarajappaDBDevaraj Basavarajappa
Open Access
Abstract
Neuropeptide Y (NPY), a sympathetic neurotransmitter, is involved in various physiological functions, and its dysregulation is implicated in several neurodegenerative diseases. Glutamate excitotoxicity, endoplasmic reticulum (ER) stress, and oxidative stress are the common mechanisms associated with numerous neurodegenerative illnesses. The present study aimed to elucidate the protective effects of NPY against glutamate toxicity and tunicamycin-induced ER stress in the human neuroblastoma SH-SY5Y cell line. We exposed the SH-SY5Y cells to glutamate and tunicamycin for two different time points and analyzed the protective effects of NPY at different concentrations. The protective effects of NPY treatments were assessed by cell viability assay, and the signalling pathway changes were evaluated by biochemical techniques such as Western blotting and immunofluorescence assays. Our results showed that treatment of SH-SY5Y cells with NPY significantly increased the viability of the cells in both glutamate toxicity and ER stress conditions. NPY treatments significantly attenuated the glutamate-induced pro-apoptotic activation of ERK1/2 and JNK/BAD pathways. The protective effects of NPY were further evident against tunicamycin-induced ER stress. NPY treatments significantly suppressed the ER stress activation by downregulating BiP, phospho-eIF2α, and CHOP expression. In addition, NPY alleviated the Akt/FoxO3a pathway in acute oxidative conditions caused by glutamate and tunicamycin in SH-SY5Y cells. Our results demonstrated that NPY is neuroprotective against glutamate-induced cell toxicity and tunicamycin-induced ER stress through anti-apoptotic actions.Keywords
Funding Information
- National Health and Medical Research Council (NHMRC) of Australia
- Perpetual Hillcrest
- Australian Vision Research (AVR)
- Macquarie University, NSW, Australia
This publication has 114 references indexed in Scilit:
- BAD overexpression inhibits cell growth and induces apoptosis via mitochondrial-dependent pathway in non-small cell lung cancerCancer Cell International, 2013
- Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamateCell Death & Disease, 2013
- Neuropeptide Y Protects Rat Cortical Neurons against β-Amyloid Toxicity and Re-establishes Synthesis and Release of Nerve Growth FactorACS Chemical Neuroscience, 2012
- A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamicsCell Death & Disease, 2011
- Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stressNature Cell Biology, 2011
- Therapeutic potential of neuropeptide Y (NPY) receptor ligandsEMBO Molecular Medicine, 2010
- Switching Akt: from survival signaling to deadly responseBioEssays, 2009
- Akt Determines Replicative Senescence and Oxidative or Oncogenic Premature Senescence and Sensitizes Cells to Oxidative ApoptosisCancer Cell, 2008
- JNK signaling in apoptosisOncogene, 2008
- Brain‐derived neurotrophic factor suppresses tunicamycin‐induced upregulation of CHOP in neuronsJournal of Neuroscience Research, 2007