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

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, Ca(2+) 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 scavenging via the NK-1 receptor.