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Cbl-b and PI3K/Akt pathway are differently involved in oxygen-glucose deprivation preconditioning in PC12 cells.

Authors: Zhang, W  Yu, H  Zou, W  Wang, YF  Liang, XF  Zhang, B  Kong, JJ  Li, P  Zhang, DD  Yin, L 
Citation: Zhang W, etal., Chin Med J (Engl). 2013 Nov;126(21):4132-8.
Pubmed: (View Article at PubMed) PMID:24229686

BACKGROUND: Transient sublethal ischemia is known as ischemic preconditioning, which enables cells and tissues to survive subsequent prolonged lethal ischemic injury. Ischemic preconditioning exerts neuroprotection through phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Cbl-b belongs to the Casitas B-lineage lymphoma (Cbl) family, and it can regulate the cell signal transduction.The roles of ubiquitin ligase Cbl-b and PI3K/Akt pathway and the relationship between them in oxygen-glucose deprivation preconditioning (OGDPC) in PC12 cells were investigated in the present study. METHODS: Oxygen and glucose deprivation (OGD) model in PC12 cells was used in the present study. The 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, nuclear staining with Hoechst 33258, and Western blotting were applied to explore the roles of Cbl-b and PI3K/Akt pathway and the relationship between them in OGDPC in PC12 cells. RESULTS: Cell viability was significantly changed by OGD and OGDPC. OGD significantly decreased cell viability compared with the control group (P < 0.05), and preconditioning could rescue this damage was demonstrated by the increase of cell viability (P < 0.05). The expression of Cbl-b was significantly increased after OGD treatment. However, the activation of Akt and GSK3beta was greatly inhibited. Preconditioning could inhibit the increase of Cbl-b caused by OGD and increase the activation of Akt and GSK3beta. LY294002, a specific inhibitor of PI3K, could effectively inhibit the increase of Akt and GSK3beta after preconditioning treatment. It partly inhibited the decrease of Cbl-b expression after preconditioning treatment. CONCLUSION: Ubiquitin ligase Cbl-b and PI3K/Akt pathway are differently involved in OGDPC in PC12 cells.

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CRRD Object Information
CRRD ID: 11038824
Created: 2016-02-29
Species: All species
Last Modified: 2016-02-29
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.