Int J Med Sci 2018; 15(10):1014-1024. doi:10.7150/ijms.25656 This issue Cite

Research Paper

Trehalose inhibits H2O2-induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation

Zhijie Gao1#, Helei Wang2#, Bo Zhang3, Xuemei Wu3, Yanfeng Zhang3, Pengfei Ge1,4, Guangfan Chi5, Jianmin Liang3,4✉

1. Department of Neurosurgery, First hospital of Jilin University, Changchun 130021, China.
2. Department of Gastrointestinal Surgery, First hospital of Jilin University, Changchun 130021, China.
3. Department of Pediatric Neurology, First hospital of Jilin University, Changchun 130021, China.
4. Research center of neuroscience, First hospital of Jilin University, Changchun 130021, China.
5. Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
#: These two authors contributed equally to this work.

Citation:
Gao Z, Wang H, Zhang B, Wu X, Zhang Y, Ge P, Chi G, Liang J. Trehalose inhibits H2O2-induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation. Int J Med Sci 2018; 15(10):1014-1024. doi:10.7150/ijms.25656. https://www.medsci.org/v15p1014.htm
Other styles

File import instruction

Abstract

Autophagy is a catabolic process to maintain intracellular homeostasis via removal of cytoplasmic macromolecules and damaged cellular organelles through lysosome-mediated degradation. Trehalose is often regarded as an autophagy inducer, but we reported previously that it could prevent ischemic insults-induced autophagic death in neurons. Thus, we further investigated in this study whether trehalose could protect human dopaminergic SH-SY5Y cells against H2O2-induced lethal autophagy. We found pretreatment with trehalose not only prevented H2O2-induced death in SH-SY5Y cells, but also reversed H2O2-induced upregulation of LC3II, Beclin1 and ATG5 and downregulation of p62. Then, we proved that either autophagy inhibitor 3MA or genetic knockdown of ATG5 prevented H2O2-triggered death in SH-SY5Y cells. These indicated that trehalose could inhibit H2O2-induced autophagic death in SH-SY5Y cells. Further, we found that trehalose inhibited H2O2-induced AMPK activation and endoplasmic reticulum (ER) stress. Moreover, inhibition of AMPK activation with compound C or alleviation of ER stress with chemical chaperone 4-PBA obviously attenuated H2O2-induced changes in autophagy-related proteins. Notably, we found that trehalose inhibited H2O2-induced increase of intracellular ROS and reduction in the activities of CAT and SOD. Consistently, our data revealed as well that mitigation of intracellular ROS levels with antioxidant NAC markedly attenuated H2O2-induced AMPK activation and ER stress. Therefore, we demonstrated in this study that trehalose prevented H2O2-induced autophagic death in SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation.

Keywords: Trehalose, Oxidative stress, Autophagy, AMPK, Endoplasmic reticulum stress


Citation styles

APA
Gao, Z., Wang, H., Zhang, B., Wu, X., Zhang, Y., Ge, P., Chi, G., Liang, J. (2018). Trehalose inhibits H2O2-induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation. International Journal of Medical Sciences, 15(10), 1014-1024. https://doi.org/10.7150/ijms.25656.

ACS
Gao, Z.; Wang, H.; Zhang, B.; Wu, X.; Zhang, Y.; Ge, P.; Chi, G.; Liang, J. Trehalose inhibits H2O2-induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation. Int. J. Med. Sci. 2018, 15 (10), 1014-1024. DOI: 10.7150/ijms.25656.

NLM
Gao Z, Wang H, Zhang B, Wu X, Zhang Y, Ge P, Chi G, Liang J. Trehalose inhibits H2O2-induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation. Int J Med Sci 2018; 15(10):1014-1024. doi:10.7150/ijms.25656. https://www.medsci.org/v15p1014.htm

CSE
Gao Z, Wang H, Zhang B, Wu X, Zhang Y, Ge P, Chi G, Liang J. 2018. Trehalose inhibits H2O2-induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation. Int J Med Sci. 15(10):1014-1024.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image