XQ‐1H attenuates ischemic injury in PC12 cells via Wnt/β‐catenin signaling though inhibition of apoptosis and promotion of proliferation. (14th August 2020)

• Record Type: Journal Article
• Authors: Xu, Dan; Li, Fengyang; Hou, Kai; Gou, Xue; Fang, Weirong; Li, Yunman
• Is Part Of: Cell biology international. Volume 44:Number 11(2020)
• Page Start: 2363
• Page End: 2369
• Publication Date: 2020-08-14
• Subjects: apoptosis -- oxygen–glucose deprivation -- proliferation -- Wnt/β‐catenin pathway -- XQ‐1H; Cytology -- Periodicals; Cells -- Periodicals; 571.605
• DOI: 10.1002/cbin.11438
• Languages: English
• ISSNs: 1065-6995

Abstract

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. Abstract : XQ‐1H protected PC12 cells against OGD/R induced injury through its anti‐apoptotic and proliferative effects, which was dependent on the Wnt/β‐catenin signaling pathway through nucleus importation of β‐catenin, inhibition of cell apoptosis and possible upregulation of Bcl‐xL, Wnt1, p‐GSK‐3β, Akt, BDNF, NGF Neuro D1, Cyclin D1 as well as reduction of Caspase‐3 expression.