Involvement of the ornithine decarboxylase/polyamine system in precondition-induced cardioprotection through an interaction with PKC in rat hearts
Involvement of the ornithine decarboxylase/polyamine system in precondition-induced cardioprotection through an interaction with PKC in rat hearts
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鸟氨酸脱羧酶/多胺系统通过与大鼠心脏 PKC 相互作用参与预处理诱导的心脏保护
DOI：
10.1007/s11010-009-0183-5
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发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
li weimin
中科院分区：
文献类型：
--
作者：
li hongzhu;zhao yajun;li hong;yang baofeng;lin yan;xu changqing;wang lina;tian ye;zhang weihua;zhang li;sun yihua;han liping;li weimin
多胺（腐胺、亚精胺和精胺）在细胞生长、分化和凋亡中发挥重要作用。蛋白激酶 C (PKC) 通过诱导鸟氨酸脱羧酶 (ODC)（多胺生物合成中的限速酶）来刺激多胺生物合成。 PKC 的激活介导缺血预处理，以减少完整心脏和离体培养心肌细胞的坏死和细胞凋亡。在这项研究中，我们检查了ODC/多胺系统是否参与缺血预处理信号通路，以及该系统是否在预处理诱导的心脏保护中与PKC相互作用。心脏经过 5 分钟缺血和 5 分钟复流的三个周期进行预处理，这导致 ODC 表达以及亚精胺、精胺和总多胺池水平增加。 α-二氟甲基鸟氨酸（DFMO）和乙基乙二醛双（脒腙）（EGBG）抑制参与多胺生物合成的关键酶，并消除预处理诱导的梗塞面积减小和缺血后心脏收缩功能的改善。它们还增加细胞凋亡程度并加重心肌超微结构损伤。抑制还减弱了预处理诱导的 PKC-δ、-ε 同种型从细胞质到颗粒的易位和激活。相反，佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 激活 PKC 上调 ODC/多胺系统，而 PKC 抑制剂白屈菜红碱 (Che) 下调 ODC/多胺系统。这些发现表明，多胺合成代谢的上调是对预处理的反应，并介导预处理诱导的心脏保护作用。 ODC/多胺系统和 PKC 信号可能会在预处理心脏中“串扰”，从而抑制一个途径会导致另一个途径活性降低，反之亦然。
Polyamines (putrescine, spermidine, and spermine) play an essential role in cell growth, differentiation, and apoptosis. Protein kinase C (PKC) stimulates polyamine biosynthesis through the induction of ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis. Activation of PKC mediates ischemic preconditioning to reduce necrosis and apoptosis in intact hearts and in isolated culture cardiomyocytes. In this study, we examined whether the ODC/polyamine system is involved in the ischemic preconditioning signaling pathway and whether this system interacts with PKC in preconditioning-induced cardioprotection. Hearts were preconditioned with three cycles of 5-min ischemia and 5-min reflow, which caused an increase of ODC expression and spermidine, spermine, and total polyamine pool levels. α-Difluoromethylornithine (DFMO) and ethylglyoxal bis (guanylhydrazone) (EGBG) inhibited the key enzymes involved in polyamine biosynthesis, and abolished the preconditioning-induced reduction in infarct size and improvement in postischemic heart contractility function. They also increased cell apoptosis extent and aggravated myocardium ultrastructure damage. Inhibition also attenuated the preconditioning-induced translocation and activation of the PKC-δ, -ε isoforms from the cytosol to the particulate. Conversely, activation of PKC by phorbol 12-myristate 13-acetate (PMA) upregulated the ODC/polyamine system, whereas the PKC inhibitor chelerythrine (Che) downregulated the ODC/polyamine system. These findings suggest that upregulation of the polyamine synthesis metabolism occurs in response to preconditioning and mediates preconditioning-induced cardioprotection. The ODC/polyamine system and PKC signals may “cross-talk” in preconditioned hearts such that inhibiting one pathway leads to a reduction in the activity of the other pathway and vice versa.
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DOI：
10.1152/ajpheart.00012.2005
发表时间：
2005-04
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
T. Okada;H. Otani;Yue Wu;Takamichi Uchiyama;S. Kyoi;R. Hattori;Tomohiko Sumida;Hiroyoshi Fujiwara;H. Imamura
通讯作者：
T. Okada;H. Otani;Yue Wu;Takamichi Uchiyama;S. Kyoi;R. Hattori;Tomohiko Sumida;Hiroyoshi Fujiwara;H. Imamura
影响因子：
3.5
作者：
Heather M. Wallace;A. Fraser
通讯作者：
Heather M. Wallace;A. Fraser
DOI：
10.1152/ajpheart.1994.266.3.h1145
发表时间：
1994-03
期刊：
The American journal of physiology
影响因子：
--
作者：
K. Ytrehus;Yongge Liu;J. Downey
通讯作者：
K. Ytrehus;Yongge Liu;J. Downey
影响因子：
20.1
作者：
Tong, HY;Chen, WN;Murphy, E
通讯作者：
Murphy, E
影响因子：
3.7
作者：
A. P. Butler;P. Mar;F. McDonald;R. Ramsay
通讯作者：
A. P. Butler;P. Mar;F. McDonald;R. Ramsay