XQ‐1H attenuates ischemic injury in PC12 cells via Wnt/β‐catenin signaling though inhibition of apoptosis and promotion of proliferation

Abstract

10-O-(N,N-dimethylaminoethyl)-ginkgolide B methanesulfonate (XQ-1H) is a new derivative of ginkgolide B and has previously been proven to exert neuroprotective effects on ischemic injury. However, it is not clear whether XQ-1H affects the cell survival and proliferation in oxygen-glucose deprivation/reoxygenation (OGD/R) damaged PC12 cells. Our results showed that OGD/R improved cell viability after 24 hr of posttreatment with XQ-1H (10 or 5 μM), inhibiting cell injury and apoptosis by upregulating the expression of brain-derived neurotrophic factor, nerve growth factor, and antiapoptotic B-cell lymphoma-extra large, while reducing proapoptotic cleaved caspase-3 protein. By introducing the Wnt/β-catenin signaling inhibitor XAV-939 and 5-bromo-2′-deoxyuridine staining, it was proved that XQ-1H promoted the proliferation of PC12 cells in a Wnt-signal-dependent manner via inhibiting the activation of glycogen synthase kinase-3β after phosphatidylinositol 3-kinase/protein kinase B signal activation, thereby activating Wnt1, β-catenin, and the expression of downstream neurogenic differentiation 1 and cyclin D1, which was comparable to Wnt/β-catenin signaling agonist 4,6-disubstituted pyrrolopyrimidine. We conclude that XQ-1H, after OGD/R damage to PC12 cells, may limit cell apoptosis in a Wnt/β-catenin signal-dependent manner, promoting cell proliferation and survival.

Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK

“…Wnt signaling and WISP1 are vital pathways during metabolic disorders and DM for the oversight of oxidative stress, programmed cell death, and non-coding RNA function (Figure 2). Wnt proteins, which are cysteine-rich glycosylated proteins, are part of the wingless pathway that can modulate cell development and survival during aging, cardiovascular disorders, tumorigenesis, organogenesis, neurodegeneration, vascular disease, inflammation, and DM [25,28,48,76,92,115,131,150,184,276,296,297,305,307,338,339,[457][458][459][460][461][462][463][464][465][466][467]. Wnt proteins that can involve Wnt1 oversee programmed cell death [105,219,278,299,339,362,387,[467][468][469][470][471][472], pancreatic β-cell development and growth [473], skeletal function [152,305,307], trophic factor protec...…”