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Int. J. Mol. Sci. 2016, 17(4), 526; doi:10.3390/ijms17040526

Melatonin Suppresses Autophagy Induced by Clinostat in Preosteoblast MC3T3-E1 Cells

1
Yonsei-Fraunhofer Medical Device Laboratory, Department of Biomedical Engineering, Yonsei University, Wonju, 26493 Gangwon-do, Korea
2
Fraunhofer Institute IKTS-MD, Maria-Reiche-Str.2, 01109 Dresden, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Irmgard Tegeder
Received: 2 March 2016 / Revised: 25 March 2016 / Accepted: 5 April 2016 / Published: 8 April 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Microgravity exposure can cause cardiovascular and immune disorders, muscle atrophy, osteoporosis, and loss of blood and plasma volume. A clinostat device is an effective ground-based tool for simulating microgravity. This study investigated how melatonin suppresses autophagy caused by simulated microgravity in preosteoblast MC3T3-E1 cells. In preosteoblast MC3T3-E1 cells, clinostat rotation induced a significant time-dependent increase in the levels of the autophagosomal marker microtubule-associated protein light chain (LC3), suggesting that autophagy is induced by clinostat rotation in these cells. Melatonin treatment (100, 200 nM) significantly attenuated the clinostat-induced increases in LC3 II protein, and immunofluorescence staining revealed decreased levels of both LC3 and lysosomal-associated membrane protein 2 (Lamp2), indicating a decrease in autophagosomes. The levels of phosphorylation of mammalian target of rapamycin (p-mTOR) (Ser2448), phosphorylation of extracellular signal-regulated kinase (p-ERK), and phosphorylation of serine-threonine protein kinase (p-Akt) (Ser473) were significantly reduced by clinostat rotation. However, their expression levels were significantly recovered by melatonin treatment. Also, expression of the Bcl-2, truncated Bid, Cu/Zn- superoxide dismutase (SOD), and Mn-SOD proteins were significantly increased by melatonin treatment, whereas levels of Bax and catalase were decreased. The endoplasmic reticulum (ER) stress marker GRP78/BiP, IRE1α, and p-PERK proteins were significantly reduced by melatonin treatment. Treatment with the competitive melatonin receptor antagonist luzindole blocked melatonin-induced decreases in LC3 II levels. These results demonstrate that melatonin suppresses clinostat-induced autophagy through increasing the phosphorylation of the ERK/Akt/mTOR proteins. Consequently, melatonin appears to be a potential therapeutic agent for regulating microgravity-related bone loss or osteoporosis. View Full-Text
Keywords: melatonin; autophagy; ERK; Akt; mTOR; clinostat; MC3T3-E1 cells melatonin; autophagy; ERK; Akt; mTOR; clinostat; MC3T3-E1 cells
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Yoo, Y.-M.; Han, T.-Y.; Kim, H.S. Melatonin Suppresses Autophagy Induced by Clinostat in Preosteoblast MC3T3-E1 Cells. Int. J. Mol. Sci. 2016, 17, 526.

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