3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (trp-P-1) is incorporated into rat splenocytes, thymocytes, and hepatocytes through monoamine transporters and induces apoptosis.
3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which is a tryptophan pyrolysate formed during cooking, induces apoptosis in rat splenocytes, thymocytes, and hepatocytes. In this study, we investigated whether Trp-P-1 is transported into these cells and causes apoptosis. Trp-P-1 was immediately incorporated into rat splenocytes, thymocytes, and hepatocytes in a dose- and time-dependent manner. Dopamine and serotonin significantly competed with the uptake of Trp-P-1 into these cells, and nomifensine and indatraline, which are inhibitors of dopamine- and serotonin-transporters, respectively, markedly suppressed the uptake of Trp-P-1. On the other hand, amino acids including tryptophan did not compete with Trp-P-1. Inhibition of monoamine transporters using nomifensine and indatraline partially suppressed Trp-P-1-induced cell death in these cells. In hepatocytes, the inhibition of transporters prevented Trp-P-1-induced morphological changes and activation of caspase-3. These results demonstrated that Trp-P-1 is incorporated into the cells through monoamine transporters and induces apoptosis.
Hashimoto
Takashi
T
Division of Life Science, Graduate School of Science and Technology, Kobe University, Japan.
Furuyashiki
Takashi
T
Sano
Takashi
T
Ito
Wakana
W
Danno
Gen-ichi
G
Kanazawa
Kazuki
K
Ashida
Hitoshi
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D002243:Carbolines / Q000378:metabolism* / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D007189:Indans / Q000494:pharmacology; D008297:Male; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008744:Methylamines / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors
D002243:Carbolines; D053148:Caspase 3; D020169:Caspases; D018765:Dopamine Uptake Inhibitors; D007189:Indans; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D008744:Methylamines; D009627:Nomifensine; D017367:Selective Serotonin Reuptake Inhibitors; C418119:indatraline; C505410:Casp3 protein, rat; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole