UT-A Urea Transporter Protein Expressed in Liver

Abstract

Abstract. In perfused rat liver, there is phloretin-inhibitable urea efflux, but whether it is mediated by the kidney UT-A urea transporter family is unknown. To determine whether cultured HepG2 cells transport urea, thiourea influx was measured. HepG2 cells had a thiourea influx rate of 1739 ± 156 nmol/g protein per min; influx was inhibited 46% by phloretin and 32% by thionicotinamide. Western analysis of HepG2 cell lysate using an antibody to UT-A1, UT-A2, and UT-A4 revealed two protein bands: 49 and 36 kD. The same bands were detected in cultured rat hepatocytes, freshly isolated rat hepatocytes, and in liver from rat, mouse, and chimpanzee. Both bands were present when analyzed by native gel electrophoresis, and deglycosylation of rat liver lysate had no effect on either band. Differential centrifugation of rat liver lysate showed that the 49-kD protein is in the membrane fraction and the 36-kD protein is in the cytoplasm. To determine whether the abundance of these UT-A proteins varies in vivo, rats were made uremic by 5/6 nephrectomy. The 49-kD protein was significantly increased 5.5-fold in livers from uremic rats compared to pair-fed control rats. It is concluded that phloretininhibitable urea flux in liver may occur via a 49-kD protein that is specifically detected by a UT-A antibody. Uremia increases the abundance of this 49-kD UT-A protein in rat liver in vivo.

Urea–Aromatic Stacking and Concerted Urea Transport: Conserved Mechanisms in Urea Transporters Revealed by Molecular Dynamics

“…Urea transporters (UTs) are a family of transmembrane proteins that allow urea to pass through cell membranes at rates much higher than that seen in typical transporters. − These are typically trimeric proteins, with each monomeric unit having one continuous pore that spans the entire membrane. Mammalian UTs can also conduct water and homologues of urea such as formamide, acetamide, and methylurea. − Although most UTs occur in kidney cells, certain UTs are known to be expressed in other tissues as well. − The modulation of urea transport through UTs has been proposed to be a strategy for treating disorders associated with imbalances in water and salt concentration in the kidney . The inhibition of urea transport can lead to an enhancement in the excretion of water as well as electrolytes through urine.…”

Estudo da via de transporte de água e/ou amônia através dos transportadores de ureia (UTs) quando expressos em oócitos da rã >i<Lithobates catesbeianus>/i<.

“…HEDIGER, 2013), e na bexiga 3 , importante para proteger o as células de um acúmulo intracelular de ureia (YANG et al, 2002). Sabe-se que, nos eritrócitos, rim e fígado, o transporte de ureia pelos UTs pode ser inibido por um flavonoide vegetal chamado floretina (KLEIN et al 1999;GEYER et al, 2013a). A floretina é uma molécula grande que possivelmente se liga às proteínas UTs, provocando uma mudança conformacional, o que altera o transporte de ureia (LEVIN;ZHOU, 2014;TOON;SOLOMOM, 1987).…”