title: 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.affiliation: Institute of Medical Research, Dongguk University College of Medicine, Gyeongju, South Korea; Department of Anatomy, Graduate School of Dongguk University College of Medicine, Gyeongju, South Korea.
authors.forename: Jongwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Dongguk University College of Medicine, Gyeongju, South Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Jung
authors.affiliation: Institute of Medical Research, Dongguk University College of Medicine, Gyeongju, South Korea; Department of Internal Medicine, Dongguk University College of Medicine, Gyeongju, South Korea. Electronic address: drmoonss@hanmail.net.
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Moon
authors.affiliation: Institute of Medical Research, Dongguk University College of Medicine, Gyeongju, South Korea. Electronic address: nansmc@hanmail.net.
authors.forename: Minchul
authors.initials: M
authors.lastname: Seo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002229:Carbenoxolone / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D002229:Carbenoxolone
keywords: Apoptosis; Carbenoxolone (CBX); Endoplasmic reticulum stress; Hypothalamus; Reactive oxygen species