L-Theanine prevents ETEC-induced liver damage by reducing intrinsic apoptotic response and inhibiting ERK1/2 and JNK1/2 signaling pathways

L-Theanine prevents ETEC-induced liver damage by reducing intrinsic apoptotic response and inhibiting ERK1/2 and JNK1/2 signaling pathways
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L-茶氨酸通过减少内在细胞凋亡反应并抑制 ERK1/2 和 JNK1/2 信号通路来预防 ETEC 诱导的肝损伤

DOI:
10.1016/j.ejphar.2017.10.050
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发表时间:
2018-01-05
影响因子:
5
通讯作者:
Chen, Dong
Chen, Dong
中科院分区:
医学2区
文献类型:
--
作者:
Gong, Zhihua;Liu, Qiuling;Chen, Dong

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L-茶氨酸(LTA; γ-谷氨酰乙基酰胺),一种从茶中分离的独特的非蛋白质衍生的氨基酸,被广泛用作功能成分和膳食补充剂。L-茶氨酸已被证实具有保肝作用,但其机制尚不清楚。本研究使用肠致病性大肠杆菌(ETEC)感染的小鼠模型研究了L-茶氨酸的体内保护作用。L-茶氨酸显著降低了升高的天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)的血清活性,这两种肝损害的生物标志物。这与肝组织显微镜观察的组织病理学图像一致。此外,与ETEC对照组相比,L-茶氨酸显著增加Bcl-2的mRNA和蛋白表达,并分别降低Bax、抗凋亡分子和促凋亡分子的表达。L-茶氨酸预处理组caspase-3裂解蛋白表达明显低于ETEC组。此外,在L-茶氨酸预处理组中观察到细胞外信号调节激酶(ERK 1/2)和c-Jun NH 2-末端激酶(JNK 1/2)MAPK磷酸化的减少。我们的研究表明,L-茶氨酸具有抗凋亡活性,这可以归因于抑制内源性细胞凋亡和MAPK磷酸化信号通路。
L-Theanine (LTA; gamma-glutamylethylamide), a peculiar non-protein-derived amino acid isolated from tea, is widely used as a functional ingredient and dietary supplement. L-Theanine has been confirmed to have hepatoprotective effects, but the underlying mechanism remains unknown. This study investigated the protective effect of L-Theanine-in vivo, using an enterotoxigenic Escherichia coli (ETEC)-infected mouse model. L-Theanine significantly decreased the elevated serum activities of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT), two biomarkers of hepatic impairment. This was consistent with histopathological images from the microscopic observation of liver tissue. In addition, L-theanine significantly increased the mRNA and protein expression of Bcl-2 and decreased the expression of Bax, anti-and pro-apoptotic molecules, respectively, compared with levels in the ETEC control group. The expression of cleaved caspase-3 protein in the group pre-treated with L-theanine was significantly lower than that in the ETEC group. Additionally, decreases in extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase(JNK1/2) MAPK phosphorylation were observed in the L-theanine pre-treated group. Our study demonstrates that L-theanine possesses anti-apoptotic activity, which can be attributed to suppression of the intrinsic mitochondria-mediated apoptosis and MAPK phosphorylation signaling pathways.