European journal of pharmacology

Apoptosis induced by 5-(N,N-hexamethylene)-amiloride in regenerating liver after partial hepatectomy.

PMID 15496288


The effects of a specific inhibitor of the Na+/H+ exchanger, 5-(N,N-hexamethylene)-amiloride (HMA), on liver regeneration after partial hepatectomy were investigated. A single injection of HMA inhibited DNA synthesis and caused apoptosis in regenerating liver. Characteristic DNA fragmentation was observed at 4 h after partial hepatectomy with HMA-injection. The activity of Jun N-terminal kinase (JNK) increased to a maximal level at 15 min after partial hepatectomy in HMA-injected rats, while it was not detected until 30 min in the control. Western blot analysis revealed that the injection of HMA markedly increased c-Jun and phosphorylated c-Jun protein levels at 30 min after partial hepatectomy. An increase in p53 was also observed at 30 min after the HMA-injection and was followed by the upregulation of p21WAF1/CIP1 protein expression at 1 h after partial hepatectomy. These results suggested that HMA induced apoptosis accompanied by the activation of JNK and the upregulation of c-Jun, p53 and p21WAF1/CIP1 expression at an early stage of liver regeneration.