Upregulations of SNAT2 and GLS‑1 Are Key Osmoregulatory Responses of Human Corneal Epithelial Cells to Hyperosmotic Stress

Dry eye syndrome (DES) affects millions of people worldwide.
However,
as the cellular responses of the corneal epithelium under hyperosmotic
stress remain unclear, this study investigated the proteomic changes
between human corneal epithelial cells (HCECs) cultured with isosmotic
and hyperosmotic media. Under hyperosmotic stress, HCECs increased
expressions of sodium-coupled neutral amino acid transporter (SNAT2),
glutaminase (GLS-1), and a few isoforms of heat shock protein and
aldo-keto reductase family 1. The expressions of SNAT2 and GLS-1 were
increased after 6 h of exposure to hyperosmotic stress but not by
glutamine deprivation. The hyperosmotic stress increased intracellular
levels of glutamine, mitochondrial superoxide, and mitochondrial membrane
potential and induced mitochondrial fission in HCECs. Thus, the intracellular
level of glutamine was elevated in the hyperosmotic stressed HCECs
via the upregulation of SNAT2. Glutamine can act as an osmolyte to
regulate the osmolarity of HCECs or be converted to glutamate by GLS-1
for the tricarboxylic acid cycle and oxidative phosphorylation to
maintain ATP production under the hyperosmotic stress-induced mitochondrial
fission. Thus, the increases in the expressions of SNAT2 and GLS-1
are key osmoregulations in HCECs upon the hyperosmotic stress and
may act as corneal biomarkers for monitoring DES progression.