AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation.
AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation.
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AMPK激活通过减少O-Glcnacylation来抵消心脏肥大。
DOI：
10.1038/s41467-017-02795-4
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发表时间：
2018-01-25
影响因子：
16.6
通讯作者：
Bertrand L
中科院分区：
文献类型：
--
作者：
Gélinas R;Mailleux F;Dontaine J;Bultot L;Demeulder B;Ginion A;Daskalopoulos EP;Esfahani H;Dubois-Deruy E;Lauzier B;Gauthier C;Olson AK;Bouchard B;Des Rosiers C;Viollet B;Sakamoto K;Balligand JL;Vanoverschelde JL;Beauloye C;Horman S;Bertrand L
AMP激活的蛋白激酶（AMPK）已被证明可以抑制心脏肥大。在这里，我们表明，次最大AMPK激活阻断心肌细胞肥大，而不影响下游目标先前建议参与，如p70核糖体S6蛋白激酶，钙调神经磷酸酶/活化T细胞核因子（NFAT）和细胞外信号调节激酶。相反，心肌细胞肥大伴随着增加的蛋白质O-GlcNAc化，其被AMPK激活逆转。通过谷氨酰胺：6-磷酸果糖氨基转移酶（GFAT）抑制剂降低O-GlcNAc化，阻断心肌细胞肥大，模拟AMPK激活。相反，O-GlcNAc酰化诱导剂抵消AMPK的抗肥大作用。在体内，AMPK激活可防止野生型小鼠心肌肥大和伴随的O-GlcNAc化升高，但在AMPKα2缺陷小鼠中则不然。用O-GlcNAc酰化诱导剂处理野生型小鼠逆转AMPK作用。最后，我们证明AMPK主要通过控制GFAT磷酸化来抑制O-GlcNAc化，从而减少蛋白质如肌钙蛋白T的O-GlcNAc化。我们的结论是AMPK激活主要通过抑制O-GlcNAc酰化来防止心肌肥厚。AMPK激活抑制心脏肥大。在这里，作者表明，这独立于先前提出的机制发生，AMPK控制转氨酶GFAT的磷酸化，从而通过减少蛋白O-GlcNAc酰化来预防心脏肥大。
AMP-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy. Here, we show that submaximal AMPK activation blocks cardiomyocyte hypertrophy without affecting downstream targets previously suggested to be involved, such as p70 ribosomal S6 protein kinase, calcineurin/nuclear factor of activated T cells (NFAT) and extracellular signal-regulated kinases. Instead, cardiomyocyte hypertrophy is accompanied by increased protein O-GlcNAcylation, which is reversed by AMPK activation. Decreasing O-GlcNAcylation by inhibitors of the glutamine:fructose-6-phosphate aminotransferase (GFAT), blocks cardiomyocyte hypertrophy, mimicking AMPK activation. Conversely, O-GlcNAcylation-inducing agents counteract the anti-hypertrophic effect of AMPK. In vivo, AMPK activation prevents myocardial hypertrophy and the concomitant rise of O-GlcNAcylation in wild-type but not in AMPKα2-deficient mice. Treatment of wild-type mice with O-GlcNAcylation-inducing agents reverses AMPK action. Finally, we demonstrate that AMPK inhibits O-GlcNAcylation by mainly controlling GFAT phosphorylation, thereby reducing O-GlcNAcylation of proteins such as troponin T. We conclude that AMPK activation prevents cardiac hypertrophy predominantly by inhibiting O-GlcNAcylation. AMPK activation inhibits cardiac hypertrophy. Here the authors show that this occurs independently of previously proposed mechanisms and that AMPK controls the phosphorylation of the aminotransferase GFAT, thereby preventing cardiac hypertrophy through the reduction of protein O-GlcNAcylation.
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影响因子：
11.1
作者：
Cannon MV;Silljé HH;Sijbesma JW;Vreeswijk-Baudoin I;Ciapaite J;van der Sluis B;van Deursen J;Silva GJ;de Windt LJ;Gustafsson JÅ;van der Harst P;van Gilst WH;de Boer RA
通讯作者：
de Boer RA
DOI：
10.1152/ajpheart.01269.2005
发表时间：
2006-07-01
影响因子：
4.8
作者：
Bertrand, L;Ginion, A;Vanoverschelde, JL
通讯作者：
Vanoverschelde, JL
影响因子：
2.1
作者：
Eguchi, Satoshi;Oshiro, Noriko;Yonezawa, Kazuyoshi
通讯作者：
Yonezawa, Kazuyoshi
影响因子：
16.6
作者：
Hart GW;Slawson C;Ramirez-Correa G;Lagerlof O
通讯作者：
Lagerlof O
影响因子：
--
作者：
Horman, Sandrine;Beauloye, Christophe;Bertrand, Luc
通讯作者：
Bertrand, Luc