Effects Of Exogenous Hydrogen Sulfide On Amyloid Precursor Protein/Beta-Amyloid Processing And The Expression Of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 In Pheochromocytoma Cells

ObjectiveTo observe the effects of exogenous hydrogen sulfide on the processing of amyloid precursor protein/β-amyloid (APP/Aβ) andβ-site amyloid precursor protein cleaving enzyme 1(BACE1) expression in pheochromocytoma (PC12) cells.MethodsPC12 cells were divided into 4 groups: control group, NaHS 50μmol/L group, NaHS 100μmol/L group and NaHS 200μmol/L group. The four groups were treated with 0, 50, 100 or 200μmol/L sodium hydrosulfide (NaHS, the horner of exogenous hydrogen sulfide), respectively. Western blot was used to detect the levels of key proteins in the metabolic process of APP, including APP, C99 and C83. ELISA method was used to analyze the levels of Aβ40 and Aβ42 in cellular culture medium. Then RT-PCR and Western blot were used to detect the levels of BACE1 mRNA and protein expression. Results1.There was no significant difference in the expression of APP protein among control group and all NaHS-induced groups(P>0.05).2. Compared with control group (C99: 0.937±0.053; C83: 0.427±0.064; Aβ40: 43.594±2.475; Aβ42: 36.812±2.480),NaHS significantly and dose-dependently decreased C99, Aβ40 and Aβ42 protein expression within experimental concentration rages in NaHS-induced groups(all P<0.05), in which were(C 99: 0.655±0.043 , 0.534±0.015 , 0.254±0.046; Aβ40 : 34.131±2.873, 26.051±3.662, 17.705±1.713; Aβ42: 30.743±1.225, 21.537±2.964,13.313±3.664), respectively. On the contrary, the NaHS-induced groups in C83 protein expression significantly and dose-dependently increased ( 0.531±0.020 , 0.737±0.034 , 1.042±0.050; all P<0.05) comparing with control group, while no significant change in Aβ42/ Aβ40 was shown in all groups(P>0.05).ConclusionsExogenous hydrogen sulfide might down-regulate the expression of key proteins in APP processing, such as C99, Aβ40 and Aβ42, and up-regulate the C83 protein expression in PC12 cells. The effect of exogenous hydrogen sulfide on APP/ Aβprocessing may derive from the downward effect of the expression of BACE1.