Abstract:

Abstract:Objective To observe the effect of hydrogen sulfide (H2S) on the processing of the amyloid precursor protein (APP) and explore the possible cellular signaling mechanisms in PC12 cells.  Methods The PC12 cells were treated with 50,100 and 200  μmol·L^-1 sodium hydrosulfide (NaHS) for 1 and 18 h. Western blotting method was used to detect the protein levels of C99,C83,APP,Akt,pAkt,ERK1/2 and pERK1/2. The level of Aβ42 in cellular culture medium was analyzed by ELISA. The specific PI3-K inhibitor,LY294002 (25 and 50  μmol·L^-1),or the specific MAPK kinase (MEK) inhibitor,PD98059 (25 and 50  μmol·L^-1),were added to the PC12 cells 30 min　prior to 50  μmol·L^-1 NaHS treatment. Then the above tests were repeated. At the same time normal control group was set up. Results Compared with normal control group,the expressions of C99 and Aβ42 were decreased(P<0.05),the expressions of C83 and pAkt and  the phosphorylation of  ERK1/2 were increased(P<0.05)in 50 μmol·L^-1 NaHS group. LY294002 but not PD98059 inhibited the above effects of NaHS. Conclusion H2S makes APP processing change from the non-amyloidogenic pathway to the amyloidogenic pathway,which may involve PI3-K/Akt signaling pathway.

Key words: hydrogen sulfide;amyloid precursor protein;phosphoinositide 3-kinase;serine threonine kinase