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01-10-2021 | Cytokines | Original Article

Interferon Gamma-Mediated Oxidative Stress Induces Apoptosis, Neuroinflammation, Zinc Ion Influx, and TRPM2 Channel Activation in Neuronal Cell Line: Modulator Role of Curcumin

Authors: Mustafa Güzel, Mustafa Nazıroğlu, Orhan Akpınar, Ramazan Çınar

Published in: Inflammation | Issue 5/2021

Abstract

Host defenses in the brain are modulated by the activation of several factors such as oxygen free radical species (ROS), Ca²⁺ influx, and TRPM2 activation, and they are well-known adverse factors in neurotoxicity and neurodegenerative diseases. Importantly, recent data indicated a protective action of curcumin (CRC) via inhibition of TRPM2 on the inflammation factors, ROS, and apoptosis in hypoxia-induced SH-SY5Y neuronal cells. However, the relationship between interferon gamma (IFNg) exposure and TRPM2 activation in the SH-SY5Y cells are not fully identified. The SH-SY5Y cells as a neuronal cell line model were used in several neuroinflammation studies. Hence, we used the SH-SY5Y cells in the current study, and they were divided into four main groups as control, CRC, IFNg, and IFNg+CRC. The data presented here indicate that IFNg induced excessive Ca²⁺ influx via activation of TRPM2. The IFNg treatment further increased cell death, cell debris amount, apoptosis, and cytokine generations (IL-1β, IL-6, and TNF-α) which were due to increased cytosolic and mitochondrial ROS generations as well as increased activations of caspase-3 and caspase-9. The expression levels of TRPM2, PARP-1, Bax, caspase-3, and caspase-9 were increased in the cells by the IFNg treatment. However, CRC treatment reduced the increase of expression levels, cytokine generations, caspase activations, ROS release, Ca²⁺ influx, cell death, and apoptosis levels via inhibition of TRPM2 in the SH-SY5Y cells that were treated with IFNg. Moreover, the treatment of TRPM2 blockers (ACA and 2-APB) potentiated the modulator effects of CRC. In conclusion, these results suggest that neuroinflammation via IFNg lead to the TRPM2 activation in the SH-SY5Y cells, whereas CRC prevents IFNg-mediated TRPM2 activation, cell death, and cytokine generations.

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Title: Interferon Gamma-Mediated Oxidative Stress Induces Apoptosis, Neuroinflammation, Zinc Ion Influx, and TRPM2 Channel Activation in Neuronal Cell Line: Modulator Role of Curcumin
Authors: Mustafa Güzel
Mustafa Nazıroğlu
Orhan Akpınar
Ramazan Çınar
Publication date: 01-10-2021
Publisher: Springer US
Keywords: Cytokines
Interferon
Published in: Inflammation / Issue 5/2021
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-021-01465-4

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