Inhibition of glycogen synthase kinase or the apoptotic protein p53 lowers the threshold of helium cardioprotection in vivo: the role of mitochondrial permeability transition.
Inhibition of glycogen synthase kinase or the apoptotic protein p53 lowers the threshold of helium cardioprotection in vivo: the role of mitochondrial permeability transition.
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DOI：
10.1213/ane.0b013e3181815b84
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发表时间：
2008-09
影响因子：
5.7
通讯作者：
Weihrauch D
中科院分区：
文献类型：
--
作者：
Pagel PS;Krolikowski JG;Pratt PF Jr;Shim YH;Amour J;Warltier DC;Weihrauch D
促存活信号激酶抑制糖原合成酶激酶-3 β（GSK-3β）活性并刺激凋亡蛋白p53降解。氦通过激活促存活激酶产生心脏保护作用，但GSK和p53抑制剂是否介导这一过程尚不清楚。我们检验了GSK或p53抑制通过线粒体通透性转换孔（mPTP）依赖性机制降低氦心脏保护阈值的假设。家兔（n = 85），用仪器进行血流动力学测量，并进行30分钟的左前降支冠状动脉（LAD）闭塞和3小时的再灌注，接受0.9%盐水（对照），或1，3，或5个周期的70%氦-30%氧，持续5分钟，并穿插5分钟的空气-氧混合物（吸入氧浓度分数= 0.30）。其他家兔在LAD闭塞前接受GSK抑制剂SB 216763（SB 21; 0.2或0.6 mg/kg）、p53抑制剂匹氟菊酯-α（PIF; 1.5或3.0 mg/kg）或SB 21（0.2 mg/kg）或PIF（1.5 mg/kg）加氦气（1个周期），存在或不存在mPTP开放剂右侧（5 mg/kg）。与对照组（44 ± 6% [n = 7]）相比，氦减少了（P < 0.05）心肌梗死面积（分别为35 ± 6 [n = 7]，25 ± 4 [n = 7]和20 ± 3% [n = 6]，1，3和5个周期）。SB 21（0.6 [n = 7]但不是0.2 mg/kg [n = 6]）和PIF（3.0 [n = 6]但不是1.5 mg/kg [n = 7]）也减少了坏死。SB 21（0.2 mg/kg）或1.5 mg/kg PIF（1.5 mg/kg）加氦（1个周期;每组n = 6）减少梗死面积的程度与单独氦的3个周期相当，并且这种心脏保护作用被黄芪甲苷阻断（每组n = 7）。GSK或p53的抑制通过体内mPTP依赖性机制降低氦诱导的预适应阈值。
Prosurvival signaling kinases inhibit glycogen synthase kinase-3β (GSK-3β) activity and stimulate apoptotic protein p53 degradation. Helium produces cardioprotection by activating prosurvival kinases, but whether GSK and p53 inhibition mediate this process is unknown. We tested the hypothesis that inhibition of GSK or p53 lowers the threshold of helium cardioprotection via a mitochondrial permeability transition pore (mPTP)-dependent mechanism. Rabbits (n = 85) instrumented for hemodynamic measurement and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion received 0.9% saline (control), or 1, 3, or 5 cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture (fraction of inspired oxygen concentration = 0.30) before LAD occlusion. Other rabbits received the GSK inhibitor SB 216763 (SB21; 0.2 or 0.6 mg/kg), the p53 inhibitor pifithrin-α (PIF; 1.5 or 3.0 mg/kg), or SB21 (0.2 mg/kg) or PIF (1.5 mg/kg) plus helium (1 cycle) before LAD occlusion in the presence or absence of the mPTP opener atractyloside (5 mg/kg). Helium reduced (P < 0.05) myocardial infarct size (35 ± 6 [n = 7], 25 ± 4 [n = 7], and 20 ± 3% [n = 6] of area at risk, 1, 3, and 5 cycles, respectively) compared with control (44 ± 6% [n = 7]). SB21 (0.6 [n = 7] but not 0.2 mg/kg [n = 6]) and PIF (3.0 [n = 6] but not 1.5 mg/kg [n = 7]) also reduced necrosis. SB21 (0.2 mg/kg) or 1.5 mg/kg PIF (1.5 mg/kg) plus helium (1 cycle; n = 6 per group) decreased infarct size to an equivalent degree as three cycles of helium alone, and this cardioprotection was blocked by atractyloside (n = 7 per group). Inhibition of GSK or p53 lowers the threshold of helium-induced preconditioning via a mPTP-dependent mechanism in vivo.
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DOI：
10.1016/s0169-328x(99)00146-1
发表时间：
1999-07-05
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Tomasevic, G;Shamloo, M;Wieloch, T
通讯作者：
Wieloch, T
影响因子：
8
作者：
Ashcroft, M;Ludwig, RL;Vousden, KH
通讯作者：
Vousden, KH
影响因子：
10.8
作者：
Matsusaka, Hidenori;Ide, Tomomi;Tsutsui, Hiroyuki
通讯作者：
Tsutsui, Hiroyuki
N6-(3-碘苄基)-腺苷-5′-N-甲基甲酰胺通过糖原合酶激酶 3β 抑制线粒体通透性转换孔开放，从而在再灌注时提供心脏保护作用
DOI：
10.1124/jpet.106.101477
发表时间：
2006-07-01
影响因子：
3.5
作者：
Park, Sung-Sik;Zhao, Hong;Xu, Zhelong
通讯作者：
Xu, Zhelong
影响因子：
3.5
作者：
Maulik, N;Sasaki, H;Das, DK
通讯作者：
Das, DK