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Generation of Cellular Reactive Oxygen Species by Activation of the EP2 Receptor Contributes to Prostaglandin E2-Induced Cytotoxicity in Motor Neuron-Like NSC-34 Cells
Joint Authors
Kosuge, Yasuhiro
Nango, Hiroshi
Miyagishi, Hiroko
Ishige, Kumiko
Ito, Yoshihisa
Kasai, Hiroki
Yanagi, Takuya
Mawatari, Takayuki
Nishiyama, Kenta
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-01-11
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease characterized by progressive degeneration of motor neurons in the central nervous system.
Prostaglandin E2 (PGE2) plays a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS.
We have shown previously that PGE2 directly induces neuronal death through activation of the E-prostanoid (EP) 2 receptor in differentiated NSC-34 cells, a motor neuron-like cell line.
In the present study, to clarify the mechanisms underlying PGE2-induced neurotoxicity, we focused on generation of intracellular reactive oxygen species (ROS) and examined the effects of N-acetylcysteine (NAC), a cell-permeable antioxidant, on PGE2-induced cell death in differentiated NSC-34 cells.
Dichlorofluorescein (DCF) fluorescence analysis of PGE2-treated cells showed that intracellular ROS levels increased markedly with time, and that this effect was antagonized by a selective EP2 antagonist (PF-04418948) but not a selective EP3 antagonist (L-798,106).
Although an EP2-selective agonist, butaprost, mimicked the effect of PGE2, an EP1/EP3 agonist, sulprostone, transiently but significantly decreased the level of intracellular ROS in these cells.
MTT reduction assay and lactate dehydrogenase release assay revealed that PGE2- and butaprost-induced cell death were each suppressed by pretreatment with NAC in a concentration-dependent manner.
Western blot analysis revealed that the active form of caspase-3 was markedly increased in the PGE2- and butaprost-treated cells.
These increases in caspase-3 protein expression were suppressed by pretreatment with NAC.
Moreover, dibutyryl-cAMP treatment of differentiated NSC-34 cells caused intracellular ROS generation and cell death.
Our data reveal the existence of a PGE2-EP2 signaling-dependent intracellular ROS generation pathway, with subsequent activation of the caspase-3 cascade, in differentiated NSC-34 cells, suggesting that PGE2 is likely a key molecule linking inflammation to oxidative stress in motor neuron-like NSC-34 cells.
American Psychological Association (APA)
Kosuge, Yasuhiro& Nango, Hiroshi& Kasai, Hiroki& Yanagi, Takuya& Mawatari, Takayuki& Nishiyama, Kenta…[et al.]. 2020. Generation of Cellular Reactive Oxygen Species by Activation of the EP2 Receptor Contributes to Prostaglandin E2-Induced Cytotoxicity in Motor Neuron-Like NSC-34 Cells. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1205051
Modern Language Association (MLA)
Kosuge, Yasuhiro…[et al.]. Generation of Cellular Reactive Oxygen Species by Activation of the EP2 Receptor Contributes to Prostaglandin E2-Induced Cytotoxicity in Motor Neuron-Like NSC-34 Cells. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1205051
American Medical Association (AMA)
Kosuge, Yasuhiro& Nango, Hiroshi& Kasai, Hiroki& Yanagi, Takuya& Mawatari, Takayuki& Nishiyama, Kenta…[et al.]. Generation of Cellular Reactive Oxygen Species by Activation of the EP2 Receptor Contributes to Prostaglandin E2-Induced Cytotoxicity in Motor Neuron-Like NSC-34 Cells. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1205051
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205051