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2658 Thrombopoietin Protects Neural Cells and Endothelial Cells from Apoptosis Via PI3K/AKT Pathway

Program: Oral and Poster Abstracts
Session: 301. Vascular Wall Biology, Endothelial Progenitor Cells, and Platelet Adhesion, Activation, and Biochemistry: Poster III
Hematology Disease Topics & Pathways:
apoptosis, cell division, Biological Processes, pathways
Monday, December 7, 2020, 7:00 AM-3:30 PM

Liang Li, PhD1*, Junyan Wang2*, Jieyu Ye, PhD2*, Liuming Yang3*, Beng H Chong, MBBS, PhD4,5 and Mo Yang1,3*

1The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
2Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
3Lianjiang People's Hospital, Lianjiang, China
4Medicine, University of New South Wales, Kogarah, Australia
5St George Hospital, Sydney, Australia

Background: Thrombopoietin (TPO) is a hematopoietic growth factor that regulates the production of platelets and stimulates production and differentiation. The expression of TPO and TPO receptor (c-mpl) in the central nervous system (CNS) has been identified. However, the role of TPO in neural cells and endothelial cells were not clear.

Methods: C17.2 and human umbilical vein endothelial (HUVEC) cells were treated with CoCl2, TPO, or TPO + CoCl2. TPO was added into the culture medium 48 h before CoCl2 treatment. The cell viability and apoptosis of each group were tested by Cell Counter Kit 8 (CCK-8) assay and flow cytometry. The expression of Caspase-3 and mitochondrial membrane potential (MMP) were then determined by flow cytometry with Caspase-3-PE and JC-1. The effect of TPO in the PI3K/AKT pathway was detected by using Western blot.

Results: TPO has a dose-dependent effect on the growth of C17.2 cells. LY-294002 pretreatment suppressed the TPO-induced AKT activation and abolished the prosurvival effect of TPO. Via the Bcl-2/BAX signaling pathway, TPO exerted an anti-apoptotic effect by suppressing mitochondria membrane potentials. We also investigated the protective effect of TPO on human endothelial cells. The cell viability of HUVECs decreased gradually with the enhancement of CoCl2 at a gradient of chemical concentrations (r= -0.997). CoCl2 dramatically increased apoptosis of HUVECs, whereas pre-treatment with TPO rescued cell apoptosis induced by CoCl2 (P<0.01). Further investigation found that TPO decreased the expression of Caspase-3 and inhibited the reduction of MMP induced by CoCl2 (P<0.05). TPO increased the activation of PI3K/AKT pathway in HUVECs.

Conclusion: TPO has a protective effect against apoptosis of neural cells and endothelial cells through activating the PI3K/AKT pathway, thus decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.

Disclosures: No relevant conflicts of interest to declare.

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