The Regulating Mechanism of Chrysophanol on Protein Level of CaM-CaMKIV to Protect PC12 Cells Against Aβ25-35-Induced Damage

Drug Design, Development and Therapy

关键词: chrysophanol;    alzheimer’s disease;    cam-camkk-camkⅳ;    p-tau;   

DOI  :  

来源: DOAJ

【 摘 要 】

Ting Ye,1,* Hua-Wu Gao,1,* Wei-Ting Xuan,1 Shu Ye,1– 3 Peng Zhou,1– 3 Xin-Quan Li,1 Yan Wang,1– 3 Hang Song,1,2 Yan-Yan Liu,1,2 Biao Cai1– 3 1School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, People’s Republic of China; 2Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei 230012, People’s Republic of China; 3Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei 230012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Yan Liu; Biao Cai Email [e-mail]; [e-mail]: To investigate the neuroprotective effect of chrysophanol (CHR) on PC12 treated with Aβ25-35, and the involved mechanism.Methods: After the establishment of an AD cell model induced by Aβ25-35, the cell survival rate was detected by MTT, cell apoptosis was assayed by Hoechst 33342 staining, mRNA expressions of calmodulin (CaM), calcium/calmodulin-dependent protein kinase kinase (CaMKK), calcium/calmodulin-dependent protein kinase IV (CaMKIV) and tau (MAPT; commonly known as tau) were determined by qRT-PCR, and protein levels of CaM, CaMKK, CaMKIV, phospho-CaMKIV (p-CaMKIV), tau and phospho-tau (p-tau) were detected by Western blot analysis.Results: When pretreated with CHR before exposure to Aβ25-35, PC12 cells showed that increased cell viability and reduced apoptosis. The qRT-PCR results indicated that the deposition of Aβ25-35 triggers a decrease in levels of CaM, CaMKK, CaMKIV, and tau in PC12 cells. In addition, Western blot results also suggested that Aβ25-35 decreases the protein expression of CaM, CaMKK, CaMKIV, p-CaMKIV, and the ratio of p-tau to tau in PC12 cells. However, the above effects were significantly alleviated after the treatment of CHR.Conclusion: CHR plays a neuroprotective role in AD though decreasing the protein level of CaM-CaMKK-CaMKIV and the expression of p-tau downstream.Keywords: chrysophanol, Alzheimer’s disease, CaM-CaMKK-CaMKIV, p-tau

【 授权许可】

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