title: Hydrogen sulfide-induced processing of the amyloid precursor protein in SH-SY5Y human neuroblastoma cells involves the PI3-K/Akt signaling pathway.
abstract: Hydrogen sulfide (H2S) has been recently categorized as a gasotransmitter, and it may be involved in the pathology of Alzheimer's disease. However, whether H2S induces amyloid precursor protein (APP) processing remains unknown. In the present study, we tested the ability of H2S to mediate APP processing in SH-SY5Y human neuroblastoma cells. We treated SH-SY5Y human neuroblastoma cells with a range of sodium hydrosulfide (H2S donor) concentrations. Western blot analysis showed that H2S increased the generation of C83 and decreased the production of C99. Meanwhile, H2S increased the levels of a disintegrin and metalloprotease 10 (ADAM10) mRNA and protein, but had no effect on TNF-α-converting enzyme (TACE, also known as ADAM17) mRNA and protein levels. H2S also induced a significant decrease of extracellular amyloid-β42 (Aβ42). Furthermore, SH-SY5Y human neuroblastoma cells were assayed for activation of the phosphoinositide 3-kinase (PI3-K) pathway. H2S activated the PI3-K pathway. Using specific inhibitor of PI3-K, we determined that the effects of H2S on APP processing and Aβ42 were blocked by LY 294002 (PI3-K inhibitor). These data indicate that H2S can induce APP processing, and this effect is dependent on activation of the PI3-K signaling pathway.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Chongqing, 400016, China, zhanghua0303@hotmail.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Feng-li
authors.initials: FL
authors.lastname: Zhao
authors.forename: Pei-feng
authors.initials: PF
authors.lastname: Qiao
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016564:Amyloid beta-Protein Precursor; D002867:Chromones; D008565:Membrane Proteins; D009025:Morpholines; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; D006862:Hydrogen Sulfide