MicroRNA-711-Induced Downregulation of Angiopoietin-1 Mediates Neuronal Cell Death

Journal of Neurotrauma
Boris SabirzhanovBogdan A Stoica

Abstract

Angiopoietin-1 (Ang-1) is a well-known endothelial growth factor, but its effects on neurons have yet to be elucidated. We show that Ang-1 is rapidly downregulated in the injured brain after controlled cortical impact (CCI), a mouse experimental traumatic brain injury (TBI) model and in etoposide-induced neuronal apoptosis in vitro. Ang-1 treatment inhibits etoposide-induced upregulation of proapoptotic B-cell lymphoma 2 (Bcl-2) family members Noxa, p53 upregulated modulator of apoptosis (Puma), Bcl-2 interacting mediator of cell death (Bim), and Bcl-2-associated X protein (Bax); reduces markers of caspase-dependent (cytochrome c release/caspase activation) and caspase-independent (apoptosis-inducing factor release) pathways; and limits neuronal cell death. Ang-1 treatment phosphorylates receptors Tunica interna endothelial cell kinase 2 (Tie2), and β1-integrin and limits the etoposide-induced decrease in protein kinase B (Akt) activity. Blocking Tie2 and β1-integrin signaling reduces Ang-1 neuroprotective effects. After both TBI and etoposide treatment microRNA (miR)-711 are upregulated, consistent with its putative role as a negative regulator of Ang-1. We show that miR-711 directly targets the Ang-1 messenger RNA (mRNA), dec...Continue Reading

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Citations

Feb 1, 2019·International Journal of Molecular Sciences·Shotaro Michinaga, Yutaka Koyama
Jul 29, 2020·Cell Death & Disease·Oleg MakarevichBogdan A Stoica
Jul 29, 2020·International Journal of Molecular Sciences·Boris SabirzhanovBogdan A Stoica
Dec 22, 2020·CNS Neuroscience & Therapeutics·Poornima VenkatMichael Chopp
Nov 18, 2020·The Journal of Head Trauma Rehabilitation·Amy A HerroldTheresa L Bender Pape

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Methods Mentioned

BETA
Transfection
immunoprecipitation
PCR
RIP

Software Mentioned

MIPAV
Prism
Elements AR
Image Lab Imaging
Fiji
VOI
GraphPad
ImageJ
MIPAV ( Medical Image Processing , Analysis , and Visualization )
NIS

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