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Open AccessArticle

Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition

by Juhyun Song 1 and Oh Yoen Kim 2,*
1
Department of Biomedical Sciences, Center for Creative Biomedical Scientists at Chonnam National University, Gwangju 61469, Korea
2
Department of Food Sciences and Nutrition, Dong-A University, 37 550beon-gil Nakdongdaero, Saha-gu, Busan 49315, Korea
*
Author to whom correspondence should be addressed.
Nutrients 2017, 9(6), 593; https://doi.org/10.3390/nu9060593
Received: 30 April 2017 / Revised: 6 June 2017 / Accepted: 8 June 2017 / Published: 10 June 2017
(This article belongs to the Special Issue Antioxidants in Health and Disease)
Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP), p53, and Bax) and ER stress markers (phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, p-IRE1, and spliced XBP1 (sXBP1)) were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1. The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 (p-ASK1) was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling. View Full-Text
Keywords: melatonin; neuroblastoma cells; insulin resistance; endoplasmic reticulum stress; cell death melatonin; neuroblastoma cells; insulin resistance; endoplasmic reticulum stress; cell death
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Song, J.; Kim, O.Y. Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition. Nutrients 2017, 9, 593.

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