BDNF secretion from C2C12 cells is enhanced by methionine restriction.
BDNF secretion from C2C12 cells is enhanced by methionine restriction.
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通过蛋氨酸限制增强了C2C12细胞的BDNF分泌。
DOI：
10.1016/j.bbrc.2020.10.017
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Antony R;Li Y
脑源性神经营养因子 (BDNF) 在骨骼肌中作为肌因子产生，在肌肉代谢中发挥作用。然而，代谢变化如何影响骨骼肌 BDNF 表达和释放仍有待充分了解。氨基酸限制（例如蛋氨酸限制（MR））被认为是另一种禁食方法。在这里，我们报道了在 C2C12 肌管中，MR 增强了 BDNF 的释放，这是使用 ELISA、RT-qPCR、细胞免疫染色和蛋白质印迹进行测量的。蛋白质转运途径的抑制阻断了 MR 增强的 BDNF 释放，证实 MR 诱导的 BDNF 释放涉及经典的蛋白质分泌途径。 MR 增加了培养基中的 L-乳酸产物，表明 MR 促进了糖酵解。 2-脱氧葡萄糖 (2-DG) 治疗减弱了乳酸的产生以及 BDNF 的释放，表明糖酵解参与了 MR 诱导的 BDNF 释放的增强。此外，用L-乳酸（糖酵解的终产物）处理，以剂量依赖性方式增强对照细胞中的BDNF基因表达和释放，表明糖酵解产生的乳酸可能介导MR增强的BDNF释放。总体而言，本研究的结果表明，MR 至少部分通过增强糖酵解和乳酸产生来促进 C2C12 肌管分泌 BDNF。
Brain derived neurotrophic factor (BDNF) is produced in skeletal muscle as a myokine that plays a role in muscle metabolism. However, how metabolic changes affect skeletal muscle BDNF expression and release remains to be fully understood. Amino acid restrictions such as methionine restriction (MR) are considered as an alternative fasting approach. Here we reported that in C2C12 myotubes, MR enhanced BDNF release, which was measured using ELISA, RT-qPCR, cell immunostaining, and Western blot. Inhibition of protein transport pathway blocked the MR enhanced BDNF release, confirming that MR-induced BDNF release involved classic protein secretory pathway. MR increased L-lactate product in media, suggesting that MR promoted glycolysis. Treatment with 2-deoxy glucose (2-DG) attenuated lactate production as well as BDNF release, suggesting that glycolysis is involved in the enhanced BDNF release induced by MR. Moreover, treatment with L-Lactate, the end-product of glycolysis, enhanced BDNF gene expression and release in control cells in a dose dependent manner, suggesting lactate produced by glycolysis may mediate the enhanced BDNF release by MR. Overall, the results of this study suggest that MR promotes BDNF secretion from C2C12 myotubes at least partially via enhancing glycolysis and lactate production.
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DOI：
10.1073/pnas.1900544116
发表时间：
2019-08-06
影响因子：
11.1
作者：
Delezie, Julien;Weihrauch, Martin;Handschin, Christoph
通讯作者：
Handschin, Christoph
影响因子：
6.1
作者：
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DOI：
10.1073/pnas.251326998
发表时间：
2001-12-04
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
15.9
作者：
ZURLO, F;LARSON, K;RAVUSSIN, E
通讯作者：
RAVUSSIN, E
影响因子：
64.5
作者：
Longchamp A;Mirabella T;Arduini A;MacArthur MR;Das A;Treviño-Villarreal JH;Hine C;Ben-Sahra I;Knudsen NH;Brace LE;Reynolds J;Mejia P;Tao M;Sharma G;Wang R;Corpataux JM;Haefliger JA;Ahn KH;Lee CH;Manning BD;Sinclair DA;Chen CS;Ozaki CK;Mitchell JR
通讯作者：
Mitchell JR