Modulation of ornithine decarboxylase activity and mitogen-activated protein kinases in protocatechualdehyde-induced apoptosis of CTLL-2 cells.
Protocatechualdehyde (PA, a dihydroxybenzene derivative) has previously been shown to induce apoptotic cell death in cytotoxic T cells (CTLL-2). However, the molecular mechanisms by which PA regulates apoptosis are still unclear. In this study, the possible roles of ornithine decarboxylase activity (ODC) and mitogen-activated protein kinases (MAPKs) in the PA-induced apoptosis process were further investigated. We demonstrated that PA inhibited ODC activity induced by IL2 in a time- and dose-dependent manner. Furthermore, the expression of ODC mRNA stimulated by IL2 was also effectively suppressed. 0.12 mM PA inhibited the activation of ERK1/2 induced by IL2 and enhanced the activation of JNK, which was abrogated by IL2. No alteration in the effect of p38 MAPK on the apoptosis process was observed in the CTLL-2 cells. PD98059 (a specific ERK1/2 inhibitor) inhibited cell growth, led to cell apoptotic death and effectively decreased ODC activity and suppressed ERK1/2 activation induced by IL2. These data indicate that PA induced apoptosis in CTLL-2 cells by two mechanisms; either via inhibiting ODC induction or interfering with MAPK signaling pathways.
Wang
Yinna
Y
Department of Biochemistry, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Zhu
Zhenyu
Z
Hasuma
Tadayoshi
T
Yano
Yoshihisa
Y
Morishima
Yoshihiro
Y
Matsui-Yuasa
Isao
I
Otani
Shuzo
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001547:Benzaldehydes / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*
D001547:Benzaldehydes; D002396:Catechols; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007376:Interleukin-2; D065108:Ornithine Decarboxylase Inhibitors; C005581:protocatechualdehyde; D020928:Mitogen-Activated Protein Kinases; D009955:Ornithine Decarboxylase; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one