Acidosis mediates the upregulation of UT-A protein in livers from uremic rats.
Liver expresses a 49-kD UT-A protein whose abundance is increased by uremia. Chronic renal failure causes acidosis; therefore, the role of acidosis in increasing UT-A abundance was tested. Rats underwent 5/6 nephrectomy, and half were given bicarbonate mixed in their food. Bicarbonate administration significantly increased blood pH. Compared with sham-operated rats, UT-A protein abundance was significantly increased by 50% in livers from uremic, acidotic rats; bicarbonate administration prevented the increase in UT-A protein. To determine whether acidosis alone would increase UT-A protein in liver, rats were made acidotic, but not uremic, by feeding them HCl. HCl-feeding significantly lowered blood pH, increased urea excretion, and increased the abundance of the 49-kD liver UT-A protein by 36% compared with pair-fed nonacidotic rats. HCl-feeding significantly increased the abundance of the 117-kD UT-A1 protein in kidney inner medulla but did not change aquaporin-2 protein. Next, rats were fed urea to determine whether elevated blood urea would increase UT-A protein. However, urea feeding had no effect on UT-A in liver or kidney inner medulla. It was, therefore, concluded that acidosis, either directly or through a change in ammonium concentration, rather than other dietary components, stimulates the upregulation of UT-A protein in liver and kidney inner medulla.
Klein
Janet D
JD
Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Rouillard
Patricia
P
Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Roberts
Brian R
BR
Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
Sands
Jeff M
JM
Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D001806:Blood Urea Nitrogen; D002352:Carrier Proteins / Q000378:metabolism*; D004032:Diet; D006851:Hydrochloric Acid / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014508:Urea / Q000008:administration & dosage / Q000494:pharmacology; D014511:Uremia / Q000378:metabolism*; D000096982:Urea Transporters
D002352:Carrier Proteins; D006851:Hydrochloric Acid; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D014508:Urea; D000096982:Urea Transporters