Expression of the Nd1 gene is down-regulated by doxorubicin at post-transcriptional level.
Doxorubicin is an anti-neoplastic agent with cardiotoxicity as a side effect. We previously demonstrated that doxorubicin treatment of mice resulted in a selective decrease in expression of the Nd1 gene, which encoded a new kelch family actin binding protein in the heart. Here we show that doxorubicin treatment also reduced the Nd1 expression in various organs of mice and cultured cell lines. The treatment of Nd1-transgenic mice and Nd1-transfectants also selectively reduced levels of the exogenous Nd1 mRNAs, whose expression was under the control of various promoters. Furthermore, the doxorubicin-induced reduction of Nd1 mRNA expression in NIH3T3 cells was inhibited by treatment of these cells with cycloheximide. Thus, the doxorubicin treatment may specifically reduce the stability of Nd1 mRNA.
Takamori
Yasuyuki
Y
Departments of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Matsudo
Yuji
Y
Fujimura
Lisa
L
Kang
Myengmo
M
Harada
Yoshitada
Y
Moriya
Hideshige
H
Tokuhisa
Takeshi
T
Hatano
Masahiko
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism*; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D047908:Intracellular Signaling Peptides and Proteins; C432129:Nd1 protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D004317:Doxorubicin