title: H2S protects PC12 cells against toxicity of corticosterone by modulation of BDNF-TrkB pathway.
abstract: Corticosterone, one of the glucocorticoids, is toxic to neurons and plays an important role in depressive-like behavior and depression. We previously showed that hydrogen sulfide (H2S), a novel physiological mediator, plays an inhibitory role in depression. However, the mechanism underlying H2S-triggered antidepressant-like role is not clearly known. Brain-derived neurotrophic factor (BDNF), a neurotrophic factor, plays a neuroprotective role that is mediated by its high-affinity tropomysin-related kinase B (TrkB) receptor. In this study, to investigate the underlying mechanism of H2S-induced antidepressant-like role, we explored whether H2S could protect neurons against corticosterone-mediated cyctotoxicity and whether this protective role of H2S was involved in the regulation of BDNF-TrkB pathway. Our data demonstrated that sodium hydrosulfide (NaHS), the donor of H2S, could prevent corticosterone-induced cytotoxicity, apoptosis, accumulation of intracellular reactive oxygen species (ROS) and loss of mitochondrial membrane potential (MMP) in PC12 cells. NaHS not only induced the up-regulation of BDNF but also prevented the down-regulation of BDNF by corticosterone. It was also found that blocking BDNF-TrkB pathway by K252a, an inhibitor of TrkB, abolished the protection of H2S against corticosterone-induced cytotoxicity, apoptosis, accumulation of ROS, and loss of MMP. These results suggest that H2S protects against the neurotoxicity of corticosterone by modulation of the BDNF-TrkB pathway.
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang 42100, China Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, University of South China, Hengyang 421001, China.
authors.forename: Shenglan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Medical College, University of South China, Hengyang 421001, China tangxq-usc@qq.com uscty@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang 42100, China Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, University of South China, Hengyang 421001, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang 42100, China Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, University of South China, Hengyang 421001, China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Gu
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang 42100, China Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, University of South China, Hengyang 421001, China Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China tangxq-usc@qq.com uscty@163.com.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003345:Corticosterone / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003863:Depression / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D016716:PC12 Cells; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D020813:Receptor, trkB; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human; D003345:Corticosterone; D006862:Hydrogen Sulfide
keywords: brain-derived neurotrophic factor; corticosterone; hydrogen sulfide; neurotoxicity; tyrosine kinase receptor B