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 scavenging via the NK-1 receptor.
Highlights
Substance P (SP), an 11-amino acid neuropeptide of the tachykinin family, has been shown broadly distributed in the central and peripheral nervous system with multiple functions in both physiological and pathological conditions[1,2,3]
Hyperosmotic stress induces the apoptosis of corneal epithelial cells To investigate the effect of hyperosmotic stress on the survival of corneal epithelial cells, we treated mouse TKE2 cells in varying osmolarities (450, 550 or 650 mOsm) medium achieved by addition of glucose for 12, 24 or 48 h
We proposed an experimental model in vitro in which corneal epithelial cells (TKE2 cells) were exposed to hyperosmolar medium achieved by addition of glucose to induced acute apoptosis
Summary
Substance P (SP), an 11-amino acid neuropeptide of the tachykinin family, has been shown broadly distributed in the central and peripheral nervous system with multiple functions in both physiological and pathological conditions[1,2,3]. Recent studies have shown that SP possesses anti-apoptotic effects in a variety of cells, such as kidney epithelial cells [6], colonocytes [7], cerebellar granule
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