|
The protective effects of dipeptidyl peptidase-4 inhibitor on
AD-like neurodegenerative changes
CHEN Shu-yi1, GUO Ai1, CHEN Yan-lin1, FU Rong-xia2, ZHAO Gang3, PENG Peng1, SONG Qi-jun1, DENG Yan-qiu1△
2017, 45 (4):
342-348.
doi: 10.11958/20161595
Objective To explore the protective effects of dipeptidyl peptidase- 4 inhibitor (DPP- 4I) on AD- like
neurodegenerative changes and its mechanism. Methods The human neuroblastoma cell line SH-SY5Y on the logarithmic
phase was divided into six groups: control group (CON group, treated with PBS contained 1‰ DMSO for 12 h), wortmannin
intervention group (W group, treated with 0.03 μmol/L wortmannin for 12 h), DPP-4I intervention group (DPP-4I group,
treated with 10 μmol/L DPP-4I for 12 h), both DPP-4I and wortmannin intervention group (DPP-4I+W group, pre-treated
with 10 μmol/L DPP-4I for 2 h, then 0.03 μmol/L wortmannin for 12 h), DPP-4I, wortmannin and Ex9-39 intervention
group (DPP-4I+W+Ex9-39 group, pre-treated with 10 μmol/L Ex9-39 for 2 h, then 10 μmol/L DPP-4I for 2 h followed by 0.03 μmol/L wortmannin for 12 h), and Ex9-39 intervention group (Ex9-39 group, treated with 10 μmol/L Ex9-39 for 12 h).
MTT assay was used to detect the cell vitality. Western blot assay was used to detect the level of total tau protein (tau-5) and
phosphorylated tau at different sites (pSpS199/202, pT231 and pS396), the level of phosphorylated neurofilaments (NF-H,
NF- M) and phosphorylation of critical enzyme in PI3K/Akt/GSK- 3β signaling pathway. Results (1) The cell vitality
decreased, the levels of pSpS199/202, pT231, pS396 and NF-H/M increased significantly in W group than those in CON
group. However, comparing with CON group, the above mentioned parameters reversed in DPP-4I group. Comparing with W
group, the cell vitality increased and phosphorylated levels of above mentioned indices were decreased in DPP-4I+W group.
(2) The cell vitality showed a decline trend while the levels of phosphorylation tau at three different sites and NF-H/M were
higher in Ex9-39 group than those in CON group. Comparing with DPP-4I+W group, the results of the phosphorylated levels
showed the same changes in DPP- 4I + W + Ex9- 39 group. (3) Comparing with CON group, the expression levels of
phosphorylated PI3K, Akt and GSK3β increased significantly in DPP- 4I group, while those decreased in W group.
Additionally, the expression levels of phosphorylated PI3K, Akt and GSK3β were significantly increased in DPP- 4I + W
group than those in W group. Conclusion DPP-4I can enhance the level of GLP-1 and activate PI3K/Akt/GSK-3β insulin
signaling pathway to improve the hyperphosphorylated tau and NFs induced by wortmannin, and to protect AD- like
neurodegeneration.
Related Articles |
Metrics
|