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PF-06409577 Activates AMPK Signaling to Protect Retinal Pigment Epithelium Cells From UV Radiation

PF-06409577 Activates AMPK Signaling to Protect Retinal Pigment Epithelium Cells From UV Radiation

Xiao-Feng Li, Xiu-Ming Liu, Da-Rui Huang, Hai-Jing Cao, Jun-Ying Wang

Biochem Biophys Res Commun. 2018 Jun 18;501(1):293-299.

PMID: 29733844

Abstract:

Ultra-violet (UV) radiation (UVR) to human retinas induces oxidative injury to the resident retinal pigment epithelium (RPE) cells. PF-06409577 a novel, potent and direct AMP-activated protein kinase (AMPK) activator. In ARPE-19 cells and primary murine RPE cells, PF-06409577 significantly inhibited UVR-induced viability reduction, cell death and apoptosis. PF-06409577 activated AMPK signaling in RPE cells by increasing AMPKα1-acetyl-CoA carboxylase phosphorylation and AMPK activity. AMPK inhibition, by AMPKα1-shRNA, -CRISPR/Cas9 knockout or -T172A dominant negative mutation, almost abolished PF-06409577-induced RPE cytoprotection against UVR. PF-06409577 enhanced nicotinamide adenine dinucleotide phosphate (NADPH) activity and expression levels of Nrf2-dependent genes in RPE cells. Furthermore, UVR-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage were largely inhibited by the AMPK activator. In summary, PF-06409577 inhibits UVR-induced oxidative stress and RPE cell death by activating AMPK signaling.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1467057233	PF-06409577		1467057-23-3	Price

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