[The effect of edaravone on MAPKs signal pathway associated with Abeta(25-35) treatment in PC12 cells].
OBJECTIVE
To explore whether edaravone protects cells damage via mitogen-activated protein kinases (MAPKs) signal pathway, and which procedure of p38 be affected so as to add theories for AD pathogenesis and treatments.


METHODS
According to different drugs treated, PC12 cells in vitro were divided into four groups. Negative control group: cells were treated with media alone. AD model group: cells were treated with 30 pmol/L Abeta(25-35). Inhibitor control group: cells were treated with 10 micromol/L SB203580 Cp38 mitogen-activated protein kinase (p38) inhibitor], 10 micromol/L SP600125 [c-Jun NH2 terminal kinase (JNK) inhibitor], or 10 micromol/L PD98059 extracelular signal regulated kinase (ERK) inhibitor]. Low-dose, middle-dose and high-dose edaravone group: cells plated for 24 hours treated with 30 micromol/L Abeta(25-35) and co-treated with 20, 40, 80 micromol/L edaravone 3 hours, respectively. The morphology of the treated cells were observed, the p-p38, p-JNK and p-ERK proteins in each group were tested by the Western blot. The p38 mRNA were tested in each group above (only add SB203580 10 micromol/L in third group) by the real time PCR.


RESULTS
(1) The p-p38 protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-p38 protein in the inhibitor group and edaravone groups was decreased significantly (P<0.05) when compared with that in model control group. The p-p38 proteins were significantly increased in the three edaravone groups compared with that in inhibiter control group (P<0.05). The p-p38 protein in middle-dose edaravone group was decreased compared with that in low-dose edaravone group (P<0.05). There was no relationship in dose-dependent manner about edaravone. Compared with three edaravone groups, the p-p38 protein was lower than it in high-dose edaravone & inhibiter group (P<0.05). (2) The p-JNK protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-JNK protein in the inhibitor group was decreased compared with that in model control group (P<0.05). (3) No significantly difference of p-ERK protein concentration was observed in other groups when compared with that in negative control group (P>0.05 each). (4) Compared with negative control group, the p38 mRNA in model control group was significantly increased, and it was significantly decreased in inhibitor control group (P<0.05 each). In 40 micromol/L and 80 micromol/L edaravone groups, the p38 mRNA was significantly decreased compared with that in model control group, and it still was decreased compared with that in inhibitor control group (P<0.05). The p38 mRNA in 40 micromol/L edaravone group was the lowest among three edaravone groups, and it was obviously different from that in 20 micromol/L and 80 micromol/L edaravone groups (P<0.05).


CONCLUSIONS
Abeta(25-35) could increase the p-p38 and p-JNK protein expression in cultured PC12 cells, but there was no obviously expression of p-ERK protein. These indicated that Abeta(25-35) might activate MAPKs signal pathway, especially p38 and JNK, and lead to PC12 cell damage. Edaravone could decrease p38 mRNA induced-Abeta(25-35), which indicated edaravone could protect PC12 cell damage via blocking p38 signal pathway in mRNA stage and protein stage simultaneously. Hence, it is promising that edaravone would be a new medicine for AD.
Gui-lian
GL
Zhang
Ying-ying
YY
Guo
Lei
L
Zhang
Ting-ting
TT
Li
Yun
Y
Du
Li
L
Yao
Wang-gang
WG
Zhang
Hai-qin
HQ
Wu
Zhu-lin
ZL
Ma
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077553:Edaravone; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats
D016229:Amyloid beta-Peptides; D000873:Anthracenes; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; C074636:amyloid beta-protein (25-35); C432165:pyrazolanthrone; C093642:SB 203580; D000077553:Edaravone; D000983:Antipyrine