Hydrogen sulfide reduces mRNA and protein levels of beta-site amyloid precursor protein cleaving enzyme 1 in PC12 cells

Hydrogen sulfide (H2S) is now identified as a new neuromodulator. Increasing evidence suggest that H2S 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 H2S on beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) expression and amyloid beta (A beta) 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 A beta 1-42 were analyzed by ELISA. We found that sodium hydrosulfide (NaHS), a H2S donor, decreased RACE-1 mRNA and protein levels and A beta 1-42 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 A beta 1-42 secretion were abolished by inhibitors of phosphatidylinositol 3-kinase (PI3-K), but not of mitogen-activated protein kinase kinases (MEK). Our data indicate that H2S reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt signaling pathways. H2S releasing drugs may have therapeutic potential in AD patients. (C) 2010 Elsevier Ltd. All rights reserved.