Glucocorticoid upregulates Na-K-ATPase alpha- and beta-mRNA via an indirect mechanism in proximal tubule cell primary cultures.
Adrenalectomy leads to the decline in the levels of renal Na-K-adenosinetriphosphatase (Na-K-ATPase) alpha- and beta-subunit protein and mRNA. Both alpha- and beta-mRNA, however, return to the control level within 1 h after corticosterone administration. Whether or not glucocorticoid acts directly on a specific segment of nephron to upregulate Na-K-ATPase has not been determined. Studies were undertaken in an attempt to elucidate this problem. Using primary cultures of renal proximal tubules, we found that 24-h treatment with dexamethasone augmented Na-K-ATPase activity and induced coordinate increase of alpha- and beta-protein and mRNA abundance dependent on the doses in the range of 10(-8) to 10(-6) M. We further demonstrated that 24-h incubation of dexamethasone (10(-7) M) enhanced Na-K-ATPase activity by 58 +/- 14%, alpha- and beta-protein abundance by 70 +/- 18 and 51 +/- 10%, and alpha- and beta-mRNA levels by 87 +/- 12 and 62 +/- 11%, respectively. The time course studies revealed that significant increase of Na-K-ATPase activity and alpha and beta-protein abundance was reached within 4 hr of dexamethasone treatment. Pretreatment of cultured proximal tubule cells with cycloheximide (20 micrograms/ml) completely inhibited dexamethasone-induced increase of Na-K-ATPase alpha- and beta-mRNA. Our results indicate that dexamethasone upregulates Na-K-ATPase in proximal tubule cells via pretranslational mechanisms, which may be mediated by proteins.
Lee
Y C
YC
Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China.
Lin
H H
HH
Tang
M J
MJ
D000818:Animals; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000145:classification / Q000235:genetics*; D015854:Up-Regulation
D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D003513:Cycloheximide; D000254:Sodium-Potassium-Exchanging ATPase