Trehalose inhibits H2 O2 -induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation

International Journal of Medical Sciences
Zhijie GaoJianmin Liang

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...Continue Reading

Citations

Mar 29, 2019·The Journal of Pharmacology and Experimental Therapeutics·Patrick A HowsonJames B Koprich
Sep 5, 2019·Basic & Clinical Pharmacology & Toxicology·Kuan LiuBin Xu
Jan 9, 2021·Life Sciences·Nyshadham S N ChaitanyaPhaniendra Alugoju
Jul 31, 2021·Journal of Biochemical and Molecular Toxicology·Rasha Abu-KhudirAfrah F Salama

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Methods Mentioned

BETA
transfection
protein assay
Electrophoresis
protein folding

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