UT-A Urea Transporter Protein in Heart

Abstract

Abstract-Urea transporters have been cloned from kidney medulla (UT-A) and erythrocytes (UT-B). We determined whether UT-A proteins could be detected in heart and whether their abundance was altered by uremia or hypertension or in human heart failure. In normal rat heart, bands were detected at 56, 51, and 39 kDa. In uremic rats, the abundance of the 56-kDa protein increased 1.9-fold compared with pair-fed, sham-operated rats, whereas the 51-and 39-kDa proteins were unchanged. We also detected UT-A2 mRNA in hearts from control and uremic rats. Because uremia is accompanied by hypertension, the effects of hypertension per se were studied in uninephrectomized deoxycorticosterone acetate salt-treated rats, where the abundance of the 56-kDa protein increased 2-fold versus controls, and in angiotensin II-infused rats, where the abundance of the 56 kDa protein increased 1.8-fold versus controls. The 51-and 39-kDa proteins were unchanged in both hypertensive models. In human left ventricle myocardium, UT-A proteins were detected at 97, 56, and 51 kDa. In failing left ventricle (taken at transplant, New York Heart Association class IV), the abundance of the 56-kDa protein increased 1.4-fold, and the 51-kDa protein increased 4.3-fold versus nonfailing left ventricle (donor hearts). We conclude that (1) multiple UT-A proteins are detected in rat and human heart; (2) the 56-kDa protein is upregulated in rat heart in uremia or models of hypertension; and (3) the rat results can be extended to human heart, where 56-and 51-kDa proteins are increased during heart failure.

Molecular Approaches to Urea Transporters

“…Western analysis shows that rat heart expresses 3 UT-A proteins: 56, 51, and 39 kD (7). Uremia increases the abundance of the 56-kD UT-A glycoprotein (7). The abundance of the 56-kD UT-A protein also increases in hypertrophic hearts from non-uremic DOCA/salt hypertensive rats, and in short-term hypertension induced by a 3 d infusion of angiotensin II (7).…”

“…Somewhat surprisingly, heart also expresses a urea transporter (7). Although the rationale is not as obvious as for kidney, red blood cells, or liver, cardiac hypertrophy is associated with an increase in polyamine synthesis (7).…”

“…Although the rationale is not as obvious as for kidney, red blood cells, or liver, cardiac hypertrophy is associated with an increase in polyamine synthesis (7). Urea is a by-product of the production of ornithine from arginine; therefore, it is possible that the heart needs a urea transporter to dispose of any urea produced within its cells (7).…”

“…Uremia increases the abundance of the 56-kD UT-A glycoprotein (7). The abundance of the 56-kD UT-A protein also increases in hypertrophic hearts from non-uremic DOCA/salt hypertensive rats, and in short-term hypertension induced by a 3 d infusion of angiotensin II (7). Rat heart expresses only a single 2.7-kb UT-A mRNA transcript (7,31), and cDNA sequencing shows that this mRNA is UT-A2b (7).…”

Evolution of urea transporters in vertebrates: adaptation to urea's multiple roles and metabolic sources

“…In the heart, it has been suggested that urea can have cardioprotective effects in both rat and dogfish, and thus the presence of UTs in the heart under normal conditions may be advantageous . Furthermore, in mammals, there is an upregulation of cardiac UT expression in pathologies promoting urea production in this tissue, such as an increased polyamine synthesis in the development of cardiac hypertrophy (Duchesne et al, 2001). …”