PF-06409577 activates AMPK signaling to protect retinal pigment epithelium cells from UV radiation
Journal Article
·
· Biochemical and Biophysical Research Communications
- Department of Ophthalmology, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian (China)
- Department of ENT, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, Huaian (China)
Highlights: • PF-06409577 protects retinal pigment epithelium (RPE) cells from ultra-violet radiation (UVR). • PF-06409577 activates AMPK signaling in RPE cells. • AMPK activation mediates PF-06409577-induced RPE cytoprotection against UVR. • PF-06409577 activates NADPH and Nrf2 signaling in RPE cells. • PF-06409577 inhibits UVR-induced oxidative injury in RPE cells. 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.
- OSTI ID:
- 23125134
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 501; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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