Wogonin Attenuates Isoprenaline-Induced Myocardial Hypertrophy in Mice by Suppressing the PI3K/Akt Pathway.
Wogonin Attenuates Isoprenaline-Induced Myocardial Hypertrophy in Mice by Suppressing the PI3K/Akt Pathway.
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汉黄芩素通过抑制 PI3K/Akt 通路减轻异丙肾上腺素诱导的小鼠心肌肥厚
DOI：
10.3389/fphar.2018.00896
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发表时间：
2018
影响因子：
5.6
通讯作者：
Sheng L
中科院分区：
文献类型：
--
作者：
Qian W;Yu D;Zhang J;Hu Q;Tang C;Liu P;Ye P;Wang X;Lv Q;Chen M;Sheng L
许多研究都集中在确定心肌肥厚的治疗靶点，以治疗相关的心脏事件。汉黄芩素是一种天然的黄酮类化合物，具有很强的抗肥大作用。了解其药理机制可能会揭示一个有效的方法来寻找治疗靶点。通过在小鼠皮下植入异丙肾上腺素微型泵或异丙肾上腺素处理H9 C2细胞复制心肌肥大。通过超声心动图和组织学检查评估心脏结构的病理变化。通过Western blot和RT-qPCR检测促肥大信号通路的信号转导及相关基因。汉黄芩素通过抑制磷脂酰肌醇3-激酶/蛋白激酶B（PI 3 K/Akt）促肥大通路，显著减轻异丙肾上腺素诱导的心肌肥厚。汉黄芩素促进PI 3 K催化亚基α（Pik 3ca）的泛素化和降解，Pik 3ca是PI 3 K的催化亚基，其被异丙肾上腺素处理上调。汉黄芩素还增加了神经前体细胞表达发育下调基因4样（Nedd 4l），Pik 3ca的泛素E3连接酶的表达。因此，汉黄芩素靶向Nedd 4l诱导Pik 3ca降解，从而逆转PI 3 K/Akt通路的过度激活，从而减轻异丙肾上腺素诱导的心肌肥大。
Many studies have focused on identifying therapeutic targets of myocardial hypertrophy for the treatment of correlative cardiac events. Wogonin is a natural flavonoid compound that displays a potent anti-hypertrophic effect. Knowledge of its pharmacological mechanisms might reveal an effective way to search for therapeutic targets. Myocardial hypertrophy was replicated by the subcutaneous implantation of an isoprenaline mini-pump in mice or isoprenaline treatment of H9C2 cells. Pathologic changes in cardiac structure were assessed by echocardiographic and histological examinations. The signaling transduction in hypertrophy-promoting pathways and the genes involved were detected by western blot and RT-qPCR. Wogonin significantly attenuated isoprenaline-induced myocardial hypertrophy in vivo and in vitro by suppressing phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) hypertrophy-promoting pathway. Wogonin promoted the ubiquitination and degradation of PI3K catalytic subunit alpha (Pik3ca), the catalytic subunit of PI3K, which was upregulated by isoprenaline treatment. Wogonin also increased the expression of neural precursor cells expressing developmentally down-regulated gene 4-like (Nedd4l), the ubiquitin E3 ligase of Pik3ca. Therefore, wogonin targets Nedd4l to induce the degradation of Pik3ca, which reverses the over-activation of the PI3K/Akt pathway and consequently relieves the isoprenaline-induced myocardial hypertrophy.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
汉黄芩素通过干扰 DAG-PKC 通路改善脂毒性诱导的培养血管平滑肌细胞凋亡
影响因子：
8.2
作者：
Liu, Yu-min;Wang, Xiong;Zhang, Jun-jian
通讯作者：
Zhang, Jun-jian
影响因子：
18.2
作者：
Krenek, Peter;Kmecova, Jana;Kyselovic, Jan
通讯作者：
Kyselovic, Jan
影响因子：
3.1
作者：
Aoyagi T;Matsui T
通讯作者：
Matsui T
影响因子：
2.9
作者：
Bullock, BP;Habener, JF
通讯作者：
Habener, JF