Suppression effects of O-demethyldemethoxycurcumin on thapsigargin triggered on endoplasmic reticulum stress in SK-N-SH cells.

Abstract

Endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Therefore, interventions that attenuate ER stress may contribute to induction in apoptotic cell death. This study aimed to evaluate the potential involvement of O-demethyldemethoxycurcumin, an analog of curcuminoids, on thapsigargin-induced apoptosis in cultured neuroblastoma (SK-N-SH) cells through the ER stress signaling pathway. The results showed that O-demethyldemethoxycurcumin reduced thapsigargin induced cell death in SK-N-SH cells and the release of lactate dehydrogenase (LDH) by decreasing the apoptotic cell death induced by thapsigargin. Consistent with these findings, O-demethyldemethoxycurcumin inhibited the thapsigargin-induced activation of cleavagecaspase-12. Moreover, O-demethyldemethoxycurcumin attenuated the intracellular Ca(2+) level and the expression of the calpain protein. O-demethyldemethoxycurcumin also downregulated the expression of ER stress signaling proteins, including the phosphorylation of PKR-like endoplasmic reticulum kinase (p-PERK), the phosphorylation of inositol-requiring enzyme 1 (p-IRE1), activating transcription factor 6 (ATF6), binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP). Our findings suggest that O-demethyldemethoxycurcumin could protect against thapsigargin-induced ER stress in SK-N-SH cells.

• Authors: Adchara Janyou, Chatchawan Changtam, Apichart Suksamrarn, Chainarong Tocharus, Jiraporn Tocharus
• Journal: Neurotoxicology (Neurotoxicology) Vol. 50 Pg. 92-100 (Sep 2015) ISSN: 1872-9711 [Electronic] Netherlands
• PMID: 26264395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• ATF6 protein, human
• Activating Transcription Factor 6
• Annexin A5
• DDIT3 protein, human
• Diarylheptanoids
• Endoplasmic Reticulum Chaperone BiP
• Enzyme Inhibitors
• Heat-Shock Proteins
• Transcription Factor CHOP
• Thapsigargin
• L-Lactate Dehydrogenase
• EIF2AK3 protein, human
• eIF-2 Kinase
• Calpain
• Curcumin
• Calcium
• demethoxycurcumin

Topics

• Activating Transcription Factor 6 (metabolism)
• Annexin A5 (metabolism)
• Apoptosis (drug effects)
• Calcium (metabolism)
• Calpain (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Curcumin (analogs & derivatives, chemistry, pharmacology)
• Diarylheptanoids
• Dose-Response Relationship, Drug
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (drug effects)
• Enzyme Inhibitors (pharmacology)
• Extracellular Fluid (drug effects, metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Heat-Shock Proteins (metabolism)
• Humans
• L-Lactate Dehydrogenase (metabolism)
• Neuroblastoma (pathology)
• Thapsigargin (pharmacology)
• Time Factors
• Transcription Factor CHOP (metabolism)
• eIF-2 Kinase (metabolism)