Premium
3,4‐dihydroxybenzalacetone and caffeic acid phenethyl ester induce preconditioning ER stress and autophagy in SH‐SY5Y cells
Author(s) -
Tomiyama Ryoichi,
Takakura Ken,
Takatou Shouhei,
Le Thuong M.,
Nishiuchi Takumi,
Nakamura Yutaka,
Konishi Tetsuya,
Matsugo Seiichi,
Hori Osamu
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26080
Subject(s) - caffeic acid phenethyl ester , unfolded protein response , autophagy , sh sy5y , endoplasmic reticulum , chemical chaperone , oxidative stress , microbiology and biotechnology , chemistry , biochemistry , biology , caffeic acid , antioxidant , neuroblastoma , cell culture , apoptosis , genetics
3,4‐dihydroxybenzalacetone (DBL) and Caffeic acid phenethyl ester (CAPE) are both catechol‐containing phenylpropanoid derivatives with diverse bioactivities. In the present study, we analyzed the ability of these compounds to activate the unfolded protein response (UPR) and the oxidative stress response. When human SH‐SY5Y neuroblastoma cells were treated with DBL or CAPE, the expression of endoplasmic reticulum (ER) stress‐related genes such as HSPA5 , HYOU1 , DDIT3 , and SEC61b increased to a larger extent in response to CAPE treatment, while that of antioxidant genes such as HMOX1 , GCLM , and NQO1 increased to a larger extent in response to DBL treatment. DNA microarray analysis confirmed the strong link of these compounds to ER stress. Regarding the mechanism, activation of the UPR by these compounds was associated with enhanced levels of oxidized proteins in the ER, and N‐acetyl cysteine (NAC), which provides anti‐oxidative effects, suppressed the induction of the UPR‐target genes. Furthermore, both compounds enhanced the expression of LC3‐II, a marker of autophagy, and 4‐Phenylbutyric acid (4‐PBA), a chemical chaperone that reduces ER stress, suppressed it. Finally, pretreatment of cells with DBL, CAPE or low doses of ER stressors protected cells against a neurotoxin 6‐hydroxydopamine (6‐OHDA) in an autophagy‐dependent manner. These results suggest that DBL and CAPE induce oxidized protein‐mediated ER stress and autophagy that may have a preconditioning effect in SH‐SY5Y cells.