A Novel Function of Lactate Transporter MCT1 in Gastric Restitution
نویسندگان
چکیده
We investigated the function of the monocarboxylate transporter MCT1 in restitution of gastric surface mucous cells. Restitution is the repair mechanism by which cells migrate to cover an injured area. Cell migration after injury is dependent upon glycolysis, which under some conditions yields the waste product lactate. We used the bioflavenoid phloretin, a known inhibitor of MCT1, to block lactate transport in migrating cells and determine the overall effect of MCT1 on restitution. We found that inhibition of MCT1 with phloretin significantly and dose-dependently inhibited restitution. Furthermore, under HCO3 −-free conditions that simultaneously inhibit the bicarbonate transporter NBC, there was a complete inhibition of restitution after injury with no effect on viability. These results suggest that MCT1 functions along with NBC to regulate intracellular pH and provide a mechanism for lactate efflux during glycolysis. Thus, this newly discovered role of MCT1 in gastric restitution could lead to novel strategies for both facilitating restitution in gastrointestinal cells after injury and inhibiting metastasis of cancer and other cells that utilize glycolysis for migration.
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