Protective effect of carbenoxolone on ER stress-induced cell death in hypothalamic neurons.

Abstract

Hypothalamic endoplasmic reticulum (ER) stress is known to be increased in obesity. Induction of ER stress on hypothalamic neurons has been reported to cause hypothalamic neuronal apoptosis and malfunction of energy balance, leading to obesity. Carbenoxolone is an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor that converts inactive glucocorticoid into an active form. In addition to its metabolic effect via enzyme inhibitory action, carbenoxolone has shown anti-apoptotic activity in several studies. In this study, the direct effects of carbenoxolone on ER stress and cell death in hypothalamic neurons were investigated. Carbenoxolone attenuated tunicamycin induced ER stress-mediated molecules such as spliced XBP1, ATF4, ATF6, CHOP, and ROS generation. In vivo study also revealed that carbenoxolone decreased tunicamycin-induced ER stress in the hypothalamus. In conclusion, the results of this study show that carbenoxolone has protective effects against tunicamycin induced-ER stress and apoptosis in hypothalamic neurons, suggesting its direct protective effects against obesity. Further study is warranted to clarify the effects of carbenoxolone on hypothalamic regulation of energy balance in obesity.

• Authors: Jongwan Kim, Eun Jung Jung, Seong-Su Moon, Minchul Seo
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 468 Issue 4 Pg. 793-9 (Dec 25 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 26577412 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Neuroprotective Agents
• Reactive Oxygen Species
• Carbenoxolone

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Carbenoxolone (administration & dosage)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Endoplasmic Reticulum (drug effects, physiology, ultrastructure)
• Hypothalamus (drug effects, physiology)
• Neurons (drug effects, physiology)
• Neuroprotective Agents
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Stress, Physiological (drug effects, physiology)