Dehydroascorbic acid-induced endoplasmic reticulum stress and leptin resistance in neuronal cells

• Published in: Biochemical and biophysical research communications Vol. 478; no. 2; pp. 716 - 720
• Main Authors: Thon, Mina, Hosoi, Toru, Ozawa, Koichiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.09.2016
• Subjects: ascorbic acid; Cell Line, Tumor; dehydroascorbic acid; Dehydroascorbic acid (DHAA); Dehydroascorbic Acid - pharmacology; diabetes; endoplasmic reticulum; Endoplasmic reticulum (ER) stress; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; endoplasmic reticulum stress; Endoplasmic Reticulum Stress - drug effects; Gene Expression Regulation; genes; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; human cell lines; Humans; Leptin; Leptin - genetics; Leptin - metabolism; Leptin - pharmacology; leptin receptors; Leptin resistance; neurons; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; obesity; oxidation; Oxidation-Reduction; pathophysiology; phosphorylation; Phosphorylation - drug effects; Signal Transduction; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Transcription Factor CHOP - genetics; Transcription Factor CHOP - metabolism; Unfolded protein response (UPR); Unfolded Protein Response - drug effects; X-Box Binding Protein 1 - genetics; X-Box Binding Protein 1 - metabolism; AA; XBP1; Endoplasmic reticulum (ER) stress; GRP78; PERK; ER; Dehydroascorbic acid (DHAA); Leptin resistance; Leptin; UPR; IRE1; CHOP; IB; DHAA; ATF6; Unfolded protein response (UPR)
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2016.08.013

Due to its anti-obesity effects, an adipocyte-derived hormone, leptin, has become important for the treatment of obesity. However, most obese subjects are in a state of leptin resistance, and endoplasmic reticulum (ER) stress is suggested to be involved in the pathophysiology of leptin resistance. Dehydroascorbic acid (DHAA), an oxidized form of vitamin C, was found to be increased in diabetes. In the present study, we investigated the possible effects of DHAA on the activation of ER stress and leptin resistance. A human neuroblastoma cell line, stably transfected with the Ob-Rb leptin receptor (SH-SY5Y-ObRb), was treated with DHAA. We found that DHAA upregulated ER stress-related genes such as GRP78, CHOP, and spliced XBP1. Moreover, leptin-induced STAT3 phosphorylation was hindered by DHAA. These results suggested that increases in the levels of DHAA might be harmful to neurons, contributing to defective leptin-responsive signaling. •Dehydroascorbic acid (DHAA) induced endoplasmic reticulum (ER) stress.•DHAA inhibited leptin-induced signaling.•DHAA may be involved in the pathophysiology of leptin resistance by inducing ER stress.