Manganese-induced apoptosis in hepatocytes after partial hepatectomy.
To investigate the apoptosis induced by manganese (Mn) in hepatocytes in vivo, rats received a single injection of manganese chloride immediately after partial hepatectomy. Characteristic DNA fragmentation was observed at 4 h after partial hepatectomy with Mn-injection. The activation of caspase-3 by Mn-injection was detected as early as 30 min and peaked at 1 h after partial hepatectomy. The activity of Jun N-terminal kinase (JNK) increased to a maximal level, which was about 10-fold the maximal level of the control, at 15 min after partial hepatectomy and this increase was maintained for 4 h in Mn-injected rats, while a transient increase was observed at 1 h in the control. No effect of the Mn-injection on the activation of p38 mitogen-activated protein kinase (MAPK) was observed. Western blot analysis revealed that the injection of Mn markedly increased c-Jun and phosphorylated c-Jun protein levels at 1 h after partial hepatectomy. An increase in p53 was also observed at 30 min after the Mn-injection and followed by the upregulation of p21(WAF1/CIP1) protein expression at 2 h after partial hepatectomy. These results suggested that the activation of JNK and the upregulation of c-Jun, p53 and p21(WAF1/CIP1) were involved in the apoptosis of hepatocytes induced by partial hepatectomy with manganese.
Suzuki
Tomoko
T
Department of Food Science and Nutrition, Nara Women's University, Nara 630 Japan.
Tsukamoto
Ikuyo
I
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D053938:DNA Fragmentation; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016755:Proto-Oncogene Proteins c-jun; D016159:Tumor Suppressor Protein p53; D008345:Manganese; D048031:JNK Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases