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

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

  • Biochem Biophys Res Commun. 2015 Dec 25;468(4):793-9. doi: 10.1016/j.bbrc.2015.11.034.
Jongwan Kim 1,  Eun Jung Jung 2,  Seong-Su Moon 3,  Minchul Seo 4
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Biochemistry, Dongguk University College of Medicine, Gyeongju, South Korea.
  • 3 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: [email protected].
  • 4 Institute of Medical Research, Dongguk University College of Medicine, Gyeongju, South Korea. Electronic address: [email protected].
PMID: 26577412 DOI: 10.1016/j.bbrc.2015.11.034
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.

Keywords

Apoptosis; Carbenoxolone (CBX); Endoplasmic reticulum stress; Hypothalamus; Reactive oxygen species.

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