Substance P Inhibits Hyperosmotic Stress-Induced Apoptosis in Corneal Epithelial Cells through the Mechanism of Akt Activation and Reactive Oxygen Species Scavenging via the Neurokinin-1 Receptor

PloS One
Lingling YangHua Gao

Abstract

Hyperosmolarity has been recognized as an important pathological factor in dry eye leading to ocular discomfort and damage. As one of the major neuropeptides of corneal innervation, substance P (SP) has been shown to possess anti-apoptotic effects in various cells. The aim of this study was to determine the capacity and mechanism of SP against hyperosmotic stress-induced apoptosis in cultured corneal epithelial cells. The cells were exposed to hyperosmotic stress by the addition of high glucose in the presence or absence of SP. The results showed that SP inhibited hyperosmotic stress-induced apoptosis of mouse corneal epithelial cells. Moreover, SP promoted the recovery of phosphorylated Akt level, mitochondrial membrane potential, Ca2+ contents, intracellular reactive oxygen species (ROS) and glutathione levels that impaired by hyperosmotic stress. However, the antiapoptotic capacity of SP was partially suppressed by Akt inhibitor or glutathione depleting agent, while the neurokinin-1 (NK-1) receptor antagonist impaired Akt activation and ROS scavenging that promoted by SP addition. In conclusion, SP protects corneal epithelial cells from hyperosmotic stress-induced apoptosis through the mechanism of Akt activation and ROS sca...Continue Reading

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Citations

Aug 23, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susmit Suvas
Nov 7, 2018·Investigative Ophthalmology & Visual Science·Barbariga MarcoFerrari Giulio
Dec 30, 2017·International Journal of Molecular Medicine·Qi-Chen YangYi Shao
Jan 27, 2019·International Journal of Molecular Sciences·Dominique MuschterSusanne Grässel
Jun 2, 2018·Journal of Ophthalmology·Sang Beom HanJodhbir S Mehta
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Aug 4, 2018·Investigative Ophthalmology & Visual Science·Deshea L HarrisPedram Hamrah
Nov 10, 2020·Cell Cycle·Hedyieh KarbasforooshanGholamreza Karimi

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Methods Mentioned

BETA
flow cytometry
confocal microscopy
Assay
FACS

Software Mentioned

Image J
FlowJo
SPSS

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis