Co-ordinated autophagy with resveratrol and γ-tocotrienol confers synergetic cardioprotection.
Co-ordinated autophagy with resveratrol and γ-tocotrienol confers synergetic cardioprotection.
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DOI：
10.1111/j.1582-4934.2009.00921.x
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发表时间：
2010-10
影响因子：
5.3
通讯作者：
Das DK
中科院分区：
文献类型：
--
作者：
Lekli I;Ray D;Mukherjee S;Gurusamy N;Ahsan MK;Juhasz B;Bak I;Tosaki A;Gherghiceanu M;Popescu LM;Das DK
这项研究比较了两种膳食植物化学物质，葡萄衍生的白藜芦醇和棕榈油衍生的γ-生育三烯酚，单独或组合，在缺血和再灌注期间对心脏保护的自噬作用。将体重在250和300 g之间的Sprague-Dawley大鼠随机分配到以下组中的一组：载体、缺血/再灌注（I/R）、白藜芦醇+ I/R、γ-生育三烯酚+ I/R、白藜芦醇+γ-生育三烯酚+ I/R。对于白藜芦醇治疗，大鼠用白藜芦醇（2.5mg/kg）管饲15天，而对于γ-生育三烯酚实验，大鼠用γ-生育三烯酚（0.3mg/kg）管饲30天。对于组合的白藜芦醇+γ-生育三烯酚实验，用γ-生育三烯酚管饲大鼠15天，然后用白藜芦醇沿着γ-生育三烯酚继续管饲15天。30天后，使离体灌注的心脏经受30分钟的整体缺血，随后再灌注2小时。我们的研究结果首次表明，至少部分地，白藜芦醇和γ-生育三烯酚的心脏保护作用（从心室性能、心肌梗死面积和心肌细胞凋亡中得到证明）是通过它们诱导自噬的能力实现的。最重要的是，白藜芦醇和γ-生育三烯酚协同作用，提供更大程度的心脏保护，同时通过激活Akt-Bcl-2存活途径产生更大量的存活信号。自噬伴随着Beclin和LC 3-II以及mTOR信号传导的激活，其被3-甲基腺嘌呤（3-MA）或渥曼青霉素抑制。透射电镜、光学显微镜和共聚焦显微镜的结果证实了自噬的存在。人们很容易推测，在缺血和再灌注期间，自噬沿着增强的生存信号有助于细胞从损伤中恢复。
This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ-tocotrienol + I/R, resveratrol +γ-tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ-tocotrienol experiments the rats were gavaged with γ-tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ-tocotrienol experiments, the rats were gavaged with γ-tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ-tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ-toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ-tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt-Bcl-2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3-II as well as mTOR signalling, which were inhibited by either 3-methyl adenine (3-MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.
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影响因子：
6.1
作者：
Dudley, Jocelyn I.;Lekli, Istvan;Das, Dipak K.
通讯作者：
Das, Dipak K.
影响因子：
11.2
作者：
Opipari, AW;Tan, LJ;Liu, JR
通讯作者：
Liu, JR
影响因子：
--
作者：
Das, Manika;Das, Samarjit;Das, Dipak K.
通讯作者：
Das, Dipak K.
DOI：
10.1152/ajpheart.01048.2007
发表时间：
2008-02-01
影响因子：
4.8
作者：
Lekli, Istvan;Szabo, Gergo;Tosaki, Arpad
通讯作者：
Tosaki, Arpad
影响因子：
3.3
作者：
Itakura, Eisuke;Kishi, Chieko;Mizushima, Noboru
通讯作者：
Mizushima, Noboru