Isolation of the Mouse Aldose Reductase Promoter and Identification of a Tonicity-responsive Element

Abstract

Aldose reductase (AR; EC 1.1.1.21) is an oxidoreductase that catalyzes the NADPH-dependent conversion of glucose to sorbitol, the first step of the polyol pathway. AR is of great interest due to its implication in the etiology of diabetic complications. In renal medullary cells, AR also plays an osmoregulatory role by accumulating sorbitol to maintain the intracellular osmotic balance during antidiuresis. We have previously cloned the AR cDNA from mouse kidney, and we report here the isolation of the mouse AR gene promoter. Transient transfection of chloramphenicol acetyltransferase reporter constructs containing various 5'-flanking regions of the mouse AR gene in CV1 cells led to the identification of a sequence spanning base pairs -1053 to -1040, required for an enhancer activity in hypertonic compared with isotonic cell culture conditions. This sequence is similar to the tonicity-responsive element first characterized in the betaine-gamma-aminobutyric acid transporter promoter.