This study is focused on the role of UCP-2 in hepatic oxidative metabolism following acute CCl4 administration to rats. UCP-2 mRNA, almost undetectable in the liver of controls, was significantly increased 24 h after CCl4 administration, peaked at 72 h and then tended to disappear. UCP-2 protein, undetectable in controls, increased 48-72 h after CCl4 treatment. Experiments with isolated liver cells indicated that in control rats UCP-2 was expressed in non-parenchymal cells and not in hepatocytes, whereas in CCl4-treated rats UCP-2 expression was induced in hepatocytes and was not affected in non-parenchymal cells. Addition of CCl4 to the culture medium of hepatocytes from control rats failed to induce UCP-2 expression. Liver mitochondria from CCl4-treated rats showed an increase of H2O2 release at 12-24 h, followed by a rise of TBARS. Vitamin E protected liver from CCl4 injury and reduced the expression of UCP-2. Treatment with GdCl3 prior to CCl4, in order to inhibit Kupffer cells, reduced TBARS and UCP-2 mRNA increase in hepatic mitochondria. Our data indicate that CCl4 induces the expression of UCP-2 in hepatocytes with a redox-dependent mechanism involving Kupffer cells. A role of UCP-2 in moderating CCl4-induced oxidative stress during tissue regeneration after injury is suggested. © 2008 Wiley-Liss, Inc.
Uncoupling protein-2 induction in rat hepatocytes after acute carbon tetrachloride liver injury
LANNI, Antonia;
2008
Abstract
This study is focused on the role of UCP-2 in hepatic oxidative metabolism following acute CCl4 administration to rats. UCP-2 mRNA, almost undetectable in the liver of controls, was significantly increased 24 h after CCl4 administration, peaked at 72 h and then tended to disappear. UCP-2 protein, undetectable in controls, increased 48-72 h after CCl4 treatment. Experiments with isolated liver cells indicated that in control rats UCP-2 was expressed in non-parenchymal cells and not in hepatocytes, whereas in CCl4-treated rats UCP-2 expression was induced in hepatocytes and was not affected in non-parenchymal cells. Addition of CCl4 to the culture medium of hepatocytes from control rats failed to induce UCP-2 expression. Liver mitochondria from CCl4-treated rats showed an increase of H2O2 release at 12-24 h, followed by a rise of TBARS. Vitamin E protected liver from CCl4 injury and reduced the expression of UCP-2. Treatment with GdCl3 prior to CCl4, in order to inhibit Kupffer cells, reduced TBARS and UCP-2 mRNA increase in hepatic mitochondria. Our data indicate that CCl4 induces the expression of UCP-2 in hepatocytes with a redox-dependent mechanism involving Kupffer cells. A role of UCP-2 in moderating CCl4-induced oxidative stress during tissue regeneration after injury is suggested. © 2008 Wiley-Liss, Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
