Hormonal regulation of the gene for the type C ecotropic retrovirus receptor in rat liver cells

Abstract

The infectibility of the regenerating rat liver by ecotropic retroviruses was studied relative to the expression of the gene coding for the ecotropic retrovirus receptor (Ecor) that functions as a cationic amino acid transporter. It is known that the gene for the receptor is expressed in primary hepatocytes and hepatoma cells but is absent in adult liver cells. Isolation of a 2.85-kb cDNA for the rat Ecor suggested that the rat viral receptor is 97% homologous to the mouse viral receptor and that it contains the envelope-binding domain that determines the host range of ecotropic murine retroviruses. This explains the efficient infection of rat cells by ecotropic retroviruses. Since cell division is required for liver cells to be infected, we determined the susceptibility of the regenerating rat liver to infection at different time points after partial hepatectomy (0 to 24 h) in relation to the presence of receptor mRNA. Infection of the liver occurred only when the liver was exposed to virus 4 h after partial hepatectomy. This time course of infection paralleled expression of the gene for the Ecor, which was rapidly induced between 2 and 6 h during liver regeneration. However, expression of the dormant receptor gene in quiescent liver cells can be induced by insulin, dexamethasone, and arginine, indicating that cell division is not required for expression of the receptor gene in liver cells. A diet high in carbohydrate (low in protein) significantly increased the concentration of receptor mRNA in liver cells, indicating that hormones play a role in the regulation of expression of this gene in vivo. We conclude that the gene for the viral receptor is expressed in the regenerating and quiescent liver when the urea cycle enzymes are down regulated. The infection of the regenerating rat liver by ecotropic retroviruses at the time point of expression of the receptor gene supports the requirement of expression of this transporter for infection.

Insulin stimulates cationic amino acid transport activity in the isolated perfused rat pancreas

“…Recent studies have shown that insulin stimulates the expression of the ecotropic retrovirus receptor (MCAT-1-system y+) in rat liver cells (Wu, Robinson, Kung & Hatzoglou, 1994), and our data suggest that insulin also activates the low-affinity variant MCAT-2A. As in the case of neutral amino acids, insulin may phosphorylate a target protein, which in its phosphorylated form induces de-repression of a membrane transporter (reviewed by Saier, Daniels, Boerner & Lin, 1988).…”

Activation of L‐arginine transport (system y+) and nitric oxide synthase by elevated glucose and insulin in human endothelial cells.

“…Insulin enhances expression of the gene for the highaffinity cationic system y+/MCAT-1 in rat liver cells (Wu et al 1994b) and increases the Vmax for L-lysine transport via a low-affinity variant MCAT-2A in rat pancreas (Mufioz, Sweiry & Mann, 1995). In the liver, expression of the system y+ gene occurs only when the activities of urea cycle enzymes are marginal, highlighting insulin's known inhibitory effect on urea cycle enzymes (Wu et al 1994b).…”

Dysfunction of the endothelial nitric oxide signalling pathway in diabetes and hyperglycaemia

“…Insulin also enhances expression of the gene for the high-affinity cationic system y+/MCAT-1 in rat liver cells (Wu, Robinson, Kung & Hatzoglou, 1994) and increases the Vmax for L-lysine transport via a low-affinity variant MCAT-2a in rat pancreas (Mufioz, Sweiry & Mann, 1995) and L-arginine transport in gastric mucosa (Contreras et al 1997). High-affinity binding sites for insulin have been characterized in human umbilical vein endothelial cells (see Porta, La Selva, Molinatti & Molinatti, 1987), and our results have now established that stimulation of system y+ transport activity by insulin is dependent on de novo protein synthesis .…”