Jun N-terminal kinase activation and upregulation of p53 and p21(WAF1/CIP1) in selenite-induced apoptosis of regenerating liver.
To investigate apoptosis induced by selenite in hepatocytes in vivo, rats received a single injection of sodium selenite immediately after partial hepatectomy. Characteristic DNA fragmentation in gel electrophoresis and in situ end-labeling and the increase in caspase-3 activity were observed at 4 h after partial hepatectomy with selenite injection. The activation of Jun N-terminal kinase (JNK) was observed as early as 15 min and increased to about 10-fold the maximal level of the control at 1 and 2 h after partial hepatectomy in selenite-injected rats, while a transient increase was observed at 1 h in the control. Western blot analysis revealed that the c-Jun and the phosphorylated c-Jun protein markedly increased after 30 min and reached a maximal level at 1 and 2 h after partial hepatectomy with selenite injection, although c-Jun and a faint band of the phosphorylated c-Jun were observed after 1 h in the control. The levels of c-jun mRNA and c-Fos protein and mRNA in selenite-injected rats also increased more than in the control. The rise in the p53 protein level after partial hepatectomy with selenite injection was followed by the upregulation of p21(WAF1/CIP1) mRNA and protein expression. These results suggested that selenite induced apoptosis accompanied by the activation of caspase-3 and JNK and the upregulation of c-jun, c-fos, p53 and p21(WAF1/CIP1) at the early stage of liver regeneration.
Nango
Rieko
R
Department of Food Science and Nutrition, Nara Women's University, Nara 630, Japan.
Terada
Chieko
C
Tsukamoto
Ikuyo
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D024443:Aspartate Aminotransferase, Cytoplasmic / Q000737:chemistry / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000737:chemistry / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics*; D006498:Hepatectomy; D007274:Injections, Intraperitoneal; D048031:JNK Mitogen-Activated Protein Kinases; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008115:Liver Regeneration / Q000187:drug effects* / Q000235:genetics; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018038:Sodium Selenite / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D024443:Aspartate Aminotransferase, Cytoplasmic; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D018038:Sodium Selenite