Curcumin-Derived J147 Protects HT22 Cells from Cell Death Under Tunicamycin-Induced Endoplasmic Reticulum Stress with CHOP Suppression Retained After ATP5A Knockdown
- 1Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi 274-8555, Chiba, Japan
- 2Department of Pharmacology, School of Dentistry at Matsudo, Nihon University, 2-870-1 Sakaechonishi, Matsudo-shi 271-8587, Chiba, Japan
- 3Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University, 1-8-14 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan
Abstract
Oxidative stress and proteotoxic endoplasmic reticulum (ER) stress are interconnected cellular stress processes implicated in neuronal injury. J147 reportedly exerts neuroprotective effects through ATP synthase α-subunit (ATP5A)-associated mitochondrial mechanisms, but whether it protects cells from death under proteotoxic ER stress through the same mechanism remains unclear. Here, we directly compared curcumin, CNB-001, and J147 under glutamate-induced oxytosis and tunicamycin (TM)-induced ER stress in murine hippocampal HT22 cells. MTT reduction assays showed that all three compounds attenuated glutamate-induced cell death, whereas only J147 protected cells from TM-induced cytotoxicity at a submicromolar range. LIVE/DEAD staining confirmed the protective effects of J147 against both stressors. At the molecular level, J147 suppressed the TM-induced upregulation of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP) at the mRNA and protein levels without suppressing the adaptive ER chaperone glucose-regulated protein 78. ATP5A knockdown attenuated glutamate-induced oxytosis but did not protect against TM-induced cell death, and J147 retained its protective effect after ATP5A knockdown. These findings support stressor-dependent protective actions of J147 involving an ATP5A-associated mechanism against oxidative stress and an ATP5A-independent mechanism associated with suppression of CHOP induction. J147 may therefore provide a useful pharmacological tool for investigating neuronal responses to interconnected oxidative and proteotoxic stress.
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BibTeX
@article{tanaka2026curcuminderived,
title = {{Curcumin-Derived J147 Protects HT22 Cells from Cell Death Under Tunicamycin-Induced Endoplasmic Reticulum Stress with CHOP Suppression Retained After ATP5A Knockdown}},
author = {Tsugumi Tanaka and Hiroshi Nango and Komugi Tsuruta and Hiroko Miyagishi and Tadashi Saigusa and Kosuke Sugawa and Yasuhiro Kosuge},
journal = {Cells},
year = {2026},
month = nov,
doi = {10.3390/cells15212005},
url = {https://www.mdpi.com/2073-4409/15/21/2005},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Curcumin-Derived J147 Protects HT22 Cells from Cell Death Under Tunicamycin-Induced Endoplasmic Reticulum Stress with CHOP Suppression Retained After ATP5A Knockdown
AU - Tsugumi Tanaka
AU - Hiroshi Nango
AU - Komugi Tsuruta
AU - Hiroko Miyagishi
AU - Tadashi Saigusa
AU - Kosuke Sugawa
AU - Yasuhiro Kosuge
PY - 2026
DA - 2026/11/03
JO - Cells
DO - 10.3390/cells15212005
UR - https://www.mdpi.com/2073-4409/15/21/2005
AB - Oxidative stress and proteotoxic endoplasmic reticulum (ER) stress are interconnected cellular stress processes implicated in neuronal injury. J147 reportedly exerts neuroprotective effects through ATP synthase α-subunit (ATP5A)-associated mitochondrial mechanisms, but whether it protects cells from death under proteotoxic ER stress through the same mechanism remains unclear. Here, we directly compared curcumin, CNB-001, and J147 under glutamate-induced oxytosis and tunicamycin (TM)-induced ER stress in murine hippocampal HT22 cells. MTT reduction assays showed that all three compounds attenuated glutamate-induced cell death, whereas only J147 protected cells from TM-induced cytotoxicity at a submicromolar range. LIVE/DEAD staining confirmed the protective effects of J147 against both stressors. At the molecular level, J147 suppressed the TM-induced upregulation of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP) at the mRNA and protein levels without suppressing the adaptive ER chaperone glucose-regulated protein 78. ATP5A knockdown attenuated glutamate-induced oxytosis but did not protect against TM-induced cell death, and J147 retained its protective effect after ATP5A knockdown. These findings support stressor-dependent protective actions of J147 involving an ATP5A-associated mechanism against oxidative stress and an ATP5A-independent mechanism associated with suppression of CHOP induction. J147 may therefore provide a useful pharmacological tool for investigating neuronal responses to interconnected oxidative and proteotoxic stress.
SN - 2073-4409
ER -