Neuroprotective Effects of Neuropeptide Y on Human Neuroblastoma SH-SY5Y Cells in Glutamate Excitotoxicity and ER Stress Conditions

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 22; p. 3665
• Main Authors: Palanivel, Viswanthram, Gupta, Vivek, Mirshahvaladi, Seyed Shahab Oddin, Sharma, Samridhi, Gupta, Veer, Chitranshi, Nitin, Mirzaei, Mehdi, Graham, Stuart L, Basavarajappa, Devaraj
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.11.2022; MDPI
• Subjects: AKT protein; Alzheimer's disease; Apoptosis; Care and treatment; Cell Line, Tumor; Cell viability; Endoplasmic reticulum; Excitotoxicity; FOXO3 protein; Glutamate; glutamate excitotoxicity; Glutamic Acid - toxicity; Health aspects; Homeostasis; Humans; Immunofluorescence; Neuroblastoma; neurodegeneration; Neurodegenerative diseases; Neurogenesis; Neuropeptide Y; Neuropeptide Y - pharmacology; Neuropeptides; Neuroprotection; Neuroprotective Agents - pharmacology; Oxidative stress; Parkinson's disease; Peptides; Physiology; Proteins; Signal transduction; Toxicity; Tunicamycin; Tunicamycin - pharmacology; tunicamycin-induced ER stress; Western blotting; Australia; United Kingdom > UK; United States > US; Germany; glutamate excitotoxicity; SH-SY5Y cells; neuroprotection; neuropeptide Y; tunicamycin-induced ER stress; neurodegeneration; oxidative stress
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11223665

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.