M.Sc Thesis

M.Sc StudentHirsch Ayal
SubjectTranscriptional and Translational Regulation of the Renal
Magnesium Channel (paracellin-1) Gene by Dietary
Magnesium Level
DepartmentDepartment of Medicine
Supervisors ASSOCIATE PROF. Israel Zelikovic
DR. Edna Efraty
Full Thesis textFull thesis text - English Version


BACKGROUND/AIMS: Renal tubular Mg(2) reabsorption is mediated predominantly by the tight junction channel protein paracellin-1 which is encoded by the gene PCLN-1. Hypermagnesemia decreases, whereas hypomagnesemia increases Mg(2) reabsorption. This study examines the role of paracellin-1 in the adaptive response of the kidney to Mg(2) availability. METHODS/RESULTS: The effect of Mg(2) availability on the human PCLN-1 (hPCLN-1) gene promoter was examined. Using a 2.5kb hPCLN-1 5'-flanking DNA sequence, we show that magnesium depletion increases and Mg(2) load decreases hPCLN-1 promoter activity in transfected OK and HEK293 cells. The effect of dietary Mg2 level on paracelin-1 mRNA and protein levels was also studied. Mice received a low-, normal- or high Mg(2) diet for up to 3 days. Mg(2)-loaded animals displayed hypermagnesemia with increasing urine Mg(2)/Ca(2) levels paralleled by a decrease in claudin-16 protein and mRNA in the kidney. Mg(2)- deprived animals developed hypomagnesemia with decreasing urine Mg(2)/Ca(2) levels associated with an increase in paracellin-1 protein and mRNA abundance. CONCLUSIONS: Changes in Mg(2) availability may influence paracellin-1 mediated Mg(2) transport at the transcriptional level. The possible involvement of the cell membrane bound Ca(2)/Mg(2) sensing receptor or the potential role of a hypothetical Mg(2) response element on the PCLN-1 promoter in the Mg(2)-induced response remains to be explored.