title: The Anti-apoptotic Effect of Ghrelin on Restraint Stress-Induced Thymus Atrophy in Mice.
abstract: Thymic atrophy is a complication that results from exposure to many environmental stressors, disease treatments, and microbial challenges. Such acute stress-associated thymic loss can have a dramatic impact on the host's ability to replenish the necessary naïve T cell output to reconstitute the peripheral T cell numbers and repertoire to respond to new antigenic challenges. We have previously reported that treatment with the orexigenic hormone ghrelin results in an increase in the number and proliferation of thymocytes after dexamethasone challenge, suggesting a role for ghrelin in restraint stress-induced thymic involution and cell apoptosis and its potential use as a thymostimulatory agent. In an effort to understand how ghrelin suppresses thymic T cell apoptosis, we have examined the various signaling pathways induced by receptor-specific ghrelin stimulation using a restraint stress mouse model. In this model, stress-induced apoptosis in thymocytes was effectively blocked by ghrelin. Western blot analysis demonstrated that ghrelin prevents the cleavage of pro-apoptotic proteins such as Bim, Caspase-3, and PARP. In addition, ghrelin stimulation activates the Akt and Mitogen-activated protein kinases (MAPK) signaling pathways in a time/dose-dependent manner. Moreover, we also revealed the involvement of the FoxO3a pathway in the phosphorylation of Akt and ERK1/2. Together, these findings suggest that ghrelin inhibits apoptosis by modulating the stress-induced apoptotic signal pathway in the restraint-induced thymic apoptosis.
authors: Global Research Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, Korea University, Seoul 02841, Korea.
authors: Jun Ho
authors: JH
authors: Lee
authors: Global Research Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, Korea University, Seoul 02841, Korea.
authors: Tae-Jin
authors: TJ
authors: Kim
authors: Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13524, Korea.
authors: Jie Wan
authors: JW
authors: Kim
authors: Department of Anatomy, School of Medicine, Ajou University, Suwon 16499, Korea.
authors: Jeong Seon
authors: JS
authors: Yoon
authors: Department of Immunology, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors: Hyuk Soon
authors: HS
authors: Kim
authors: Global Research Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, Korea University, Seoul 02841, Korea.
authors: Kyung-Mi
authors: KM
authors: Lee
keywords: Apoptosis; Ghrelin; Restraint stress; Thymic atrophy