<p>The Regulating Mechanism of Chrysophanol on Protein Level of CaM-CaMKIV to Protect PC12 Cells Against Aβ_25-35-Induced Damage</p>

Abstract

Objective To investigate the neuroprotective effect of chrysophanol (CHR) on PC12 treated with Aβ 25-35 , and the involved mechanism. Methods After the establishment of an AD cell model induced by Aβ 25-35 , 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 Aβ 25-35 , PC12 cells showed that increased cell viability and reduced apoptosis. The qRT-PCR results indicated that the deposition of Aβ 25-35 triggers a decrease in levels of CaM, CaMKK, CaMKIV, and tau in PC12 cells. In addition, Western blot results also suggested that Aβ 25-35 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.

TRPV1 Modulator Ameliorates Alzheimer-Like Amyloid-β Neuropathology via Akt/Gsk3β-Mediated Nrf2 Activation in the Neuro-2a/APP Cell Model

“…CaMKII is mainly distributed postsynaptically; aberrant activity thereof can cause synaptic dysfunction, leading to the cognitive deficits seen during AD progression [ 57 ]. Moreover, the expression and phosphorylation of CaMKIV are elevated by A β peptide treatment of PC12 cells [ 58 ]. CaMKIV also functions to regulate calcium-dependent gene transcription, such as that involving cAMP response element binding (CREB) protein [ 42 ].…”