Activation of the PKA Signaling Pathway Stimulates Oxalate Transport by Human Intestinal Caco2-BBE Cells.

Activation of the PKA Signaling Pathway Stimulates Oxalate Transport by Human Intestinal Caco2-BBE Cells. Am J Physiol Cell Physiol. 2019 Dec 11;: Authors: Arvans D, Alshaikh A, Bashir M, Weber C, Hassan H Abstract Most kidney stones are composed of calcium oxalate, and small increases in urine oxalate enhance the stone risk. The mammalian intestine plays a crucial role in oxalate homeostasis and we had recently reported that Oxalobacter-derived factors stimulate oxalate transport by human intestinal Caco2-BBE (C2) cells through PKA activation. We therefore evaluated whether intestinal oxalate transport is directly regulated by PKA activation. To this end, PKA is activated with forskolin and IBMX (F/I). F/I significantly stimulated (3.7-fold) 14C-oxalate transport by C2 cells (≥ 49% of which is mediated by the oxalate transporter SLC26A6 [A6]), an effect completely blocked by the PKA inhibitor H89, indicating that it is PKA-dependent. PKA stimulation of intestinal oxalate transport is not cell-line specific since F/I similarly stimulated oxalate transport by the human intestinal T84 cells. F/I significantly increased (2.5-fold) A6 surface protein expression using immunocytochemistry. Assessing 14C-oxalate transport as a function of increasing 14C-oxalate concentration in the flux medium showed that that the observed stimulation is due to F/I-induced increase (1.8-fold) in Vmax and reduction (2-fold) in Km. siRNA knockdown studies s...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research