Butyrate and TGF-beta downregulate Na,K-ATPase expression in cultured proximal tubule cells.
Attempts were made to examine the effect of growth inhibitors on regulation of Na,K-ATPase in primary cultures of renal proximal tubule cells. We observed that both TGF-beta and butyrate induced dose dependent decrease of Na,K-ATPase activity. The time course studies showed that the effect of TGF-beta preceded the effect of butyrate on inhibition of Na,K-ATPase activity. Both butyrate- and TGF-beta-induced inhibition of this enzyme were in general mediated by transcriptional decreases of alpha and beta mRNA and therefore also protein abundance. Like its effect on Na,K-ATPase activity, TGF-beta compared to butyrate induced much earlier decline in Na,K-ATPase alpha and beta mRNA and protein abundance. Butyrate did not affect gene expression of TGF-beta and anti-TGF-beta antibody had no effect on butyrate-induced inhibition of DNA synthesis. Obviously, both butyrate and TGF-beta can inhibit the expression of Na,K-ATPase alpha and beta mRNA, but TGF-beta does not mediate butyrate's effect.
Tang
M J
MJ
Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan, R.O.C.
Wang
Y K
YK
Lin
H H
HH
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D007700:Kinetics; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D002087:Butyrates; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D020148:Butyric Acid; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D004247:DNA; D000254:Sodium-Potassium-Exchanging ATPase