title: Hydrogen sulfide reduces mRNA and protein levels of β-site amyloid precursor protein cleaving enzyme 1 in PC12 cells.
abstract: Hydrogen sulfide (H(2)S) is now identified as a new neuromodulator. Increasing evidence suggest that H(2)S may play an important role in the progression of Alzheimer's disease (AD). The aim of the present study is to investigate the effects of H(2)S on beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) expression and amyloid beta (Aβ) secretion in PC12 cells. The levels of BACE-1 mRNA were measured by quantitative polymerase chain reaction analysis. BACE-1 protein levels were assessed by Western blot. Cellular culture medium levels of Aβ1-42 were analyzed by ELISA. We found that sodium hydrosulfide (NaHS), a H(2)S donor, decreased BACE-1 mRNA and protein levels and Aβ1-42 release. Furthermore, NaHS promoted the phosphorylation of Akt and ERK but not JNK or p38 MAPK. However, the effects of NaHS on BACE-1 expression and Aβ1-42 secretion were abolished by inhibitors of phosphatidylinositol 3-kinase (PI3-K), but not of mitogen-activated protein kinase kinases (MEK). Our data indicate that H(2)S reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt signaling pathways. H(2)S releasing drugs may have therapeutic potential in AD patients.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Fengli
authors.initials: F
authors.lastname: Zhao
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Dai
authors.forename: Tao
authors.initials: T
authors.lastname: Meng
authors.forename: Shengfen
authors.initials: S
authors.lastname: Tu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; D006862:Hydrogen Sulfide