title: Hydrogen sulfide inhibits homocysteine-induced endoplasmic reticulum stress and neuronal apoptosis in rat hippocampus via upregulation of the BDNF-TrkB pathway.
abstract: OBJECTIVE
  Homocysteine (Hcy) can elicit neuronal cell death, and hyperhomocysteinemia is a strong independent risk factor for Alzheimer's disease. The aim of this study was to examine the effects of hydrogen sulfide (H2S) on Hcy-induced endoplasmic reticulum (ER) stress and neuronal apoptosis in rat hippocampus.
  
  
  METHODS
  Adult male SD rats were intracerebroventricularly (icv) injected with Hcy (0.6 μmol/d) for 7 d. Before Hcy injection, the rats were treated with NaHS (30 or 100 μmol·kg(-1)·d(-1), ip) and/or k252a (1 μg/d, icv) for 2 d. The apoptotic neurons were detected in hippocampal coronal slices with TUNEL staining. The expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase-12, and BDNF in the hippocampus were examined using Western blotting assays. The generation of H2S in the hippocampus was measured with the NNDPD method.
  
  
  RESULTS
  Hcy markedly inhibited the production of endogenous H2S and increased apoptotic neurons in the hippocampus. Furthermore, Hcy induced ER stress responses in the hippocampus, as indicated by the upregulation of GRP78, CHOP, and cleaved caspase-12. Treatment with the H2S donor NaHS increased the endogenous H2S production and BDNF expression in a dose-dependent manner, and significantly reduced Hcy-induced neuronal apoptosis and ER stress responses in the hippocampus. Treatment with k252a, a specific inhibitor of TrkB (the receptor of BDNF), abolished the protective effects of NaHS against Hcy-induced ER stress in the hippocampus.
  
  
  CONCLUSIONS
  H2S attenuates ER stress and neuronal apoptosis in the hippocampus of Hcy-treated rats via upregulating the BDNF-TrkB pathway.
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Wei
authors.affiliation: Laboratory Center of Biochemistry and Molecular Biology, University of South China, Hengyang 421001, China.
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Xu
authors.affiliation: 1] Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China [2] Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China.
authors.forename: Man-Hong
authors.initials: MH
authors.lastname: Li
authors.affiliation: 1] Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China [2] Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Tang
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 Anthropotomy, Medical College, University of South China, Hengyang 421001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Medical College, University of South China, Hengyang 421001, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D020138:Hyperhomocysteinemia / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D006710:Homocysteine; D020813:Receptor, trkB; D006862:Hydrogen Sulfide
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