Detection of biomarkers for apoptosis in rat liver after perfusion with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1).
We previously demonstrated that 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) induced apoptosis in primary cultured rat hepatocytes. In this study, we investigated apoptotic biomarkers in rat liver after perfusion with 30 microM Trp-P-1 as preliminary experiments for in vivo study. Induction of c-Myc and p53 protein and the activities of caspase-3, -6, and -8 were detected in Trp-P-1-perfused liver. In addition, Trp-P-1 modulated the DNA binding activity of the apoptosis-related transcription factors, NF-kappaB and AP-1. These results imply a possibility that Trp-P-1 would induce apoptosis in vivo.
Ashida
H
H
Department of Biofunctional Chemistry, Faculty of Agriculture, Kobe University, Japan. ashida@kobe-u.ac.jp
Kihara
K
K
Shiotani
B
B
Hashimoto
T
T
Kanazawa
K
K
Danno
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000032:analysis; D002243:Carbolines / Q000008:administration & dosage / Q000633:toxicity*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D053178:Caspase 6; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D010477:Perfusion; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D015415:Biomarkers; D002243:Carbolines; D015853:Cysteine Proteinase Inhibitors; D009153:Mutagens; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; C505410:Casp3 protein, rat; C505518:Casp6 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053178:Caspase 6; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole