title: Hydrogen sulfide prevents Abeta-induced neuronal apoptosis by attenuating mitochondrial translocation of PTEN.
abstract: Neuronal cell apoptosis is an important pathological change in Alzheimer's disease (AD). Hydrogen sulfide (H(2)S) is known to be a novel gaseous signaling molecule and a cytoprotectant in many diseases including AD. However, the molecular mechanism of the antiapoptosis activity of H(2)S in AD is not yet fully understood. The aim of the present study is to evaluate the inhibitory effects of H(2)S on Abeta (Aβ)-induced apoptosis and the molecular mechanisms underlying primary neuron cells. Our results showed that sodium hydrosulfide (NaHS), a donor of H(2)S, significantly ameliorated Aβ-induced cell apoptosis. NaHS also reversed the Aβ-induced translocation of the phosphatase and tensin homologs deleted on chromosome 10 (PTEN) from the cytosol to the mitochondria. Furthermore, H(2)S increased the level of p-AKT/AKT significantly. Interestingly, the antiapoptosis effects of H(2)S were blocked down by specific PI3K/AKT inhibitor wortmannin. In conclusion, these data indicate that H(2)S inhibits Aβ-induced neuronal apoptosis by attenuating mitochondrial translocation of PTEN and that activation of PI3K/AKT signaling pathway plays a critical role in H(2)S-mediated neuronal protection. Our findings provide a novel route into the molecular mechanisms of neuronal apoptosis in AD.
authors.affiliation: Henan Key Laboratory of Medical Tissue Regeneration, Department of Human Anatomy, Xinxiang Medical University, Xinxiang, Henan 453003, China. Electronic address: weigangcui1978@126.com.
authors.forename: Weigang
authors.initials: W
authors.lastname: Cui
authors.affiliation: Henan Key Laboratory of Medical Tissue Regeneration, Department of Human Anatomy, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Undergraduate Students of Basic Medicine School, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Yang
authors.affiliation: Undergraduate Students of Basic Medicine School, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Undergraduate Students of Basic Medicine School, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Henan Key Laboratory of Medical Tissue Regeneration, Department of Human Anatomy, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000730:Androstadienes / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000008:administration & dosage; D000077191:Wortmannin
chemical_list: D016229:Amyloid beta-Peptides; D000730:Androstadienes; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013440:Sulfides; C074636:amyloid beta-protein (25-35); D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C025451:sodium bisulfide; D000077191:Wortmannin; D006862:Hydrogen Sulfide
keywords: Alzheimer’s disease; PI3K; PTEN; apoptosis; hydrogen sulfide