Dietary oxidized tyrosine (O-Tyr) stimulates TGF-β1-induced extracellular matrix production via the JNK/p38 signaling pathway in rat kidneys
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- 作者：Zhuqing Leslie Li ; Yonghui Shi ; Yinyi Ding ; Yumei Ran ; Guowei Le
- 关键词：Inflammation ; MAPKs ; Oxidative stress ; Oxidized tyrosine ; Renal fibrosis ; TGF ; β1/Smads
- 刊名：Amino Acids
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：49
- 期：2
- 页码：241-260
- 全文大小：
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biochemistry, general; Analytical Chemistry; Biochemical Engineering; Life Sciences, general; Proteomics; Neurobiology;
- 出版者：Springer Vienna
- ISSN：1438-2199
- 卷排序：49
文摘
Oxidized tyrosine (O-Tyr) products have been detected in commercial food and have been demonstrated to induce liver injury in our previous study, but the precise mechanisms of the impact induced by dietary O-Tyr are still unclear. Kidney plays an important role in the metabolism of protein. Accumulation of O-Tyr products, especially the dityrosine (Dityr) and advanced oxidation protein products (AOPPs), in vivo was shown to be associated with many kidney diseases. Therefore, this study determined whether chronic exposure to dietary O-Tyr impaired renal function in rats. After O-Tyr treatment for 24 weeks, rats exhibited oxidative stress and protein oxidation in the kidneys, accompanied with inflammatory reaction and renal dysfunction. Elevated extracellular matrix (ECM) contents and the histological examination (HE and Masson stain) results indicated renal fibrosis. The Real-time PCR and Western blotting assay showed that O-Tyr activated phosphorylation of JNK/p38 and up-regulated the expression of transforming growth factor-β1 (TGF-β1) and Smad 2/3. These results suggest that dietary O-Tyr could induce oxidative stress, inflammation and renal fibrosis through JNK/p38/TGF-β1 signaling pathway. Dityr (accounting for 22 % of the total O-Tyr material) may be responsible for the O-Tyr-induced injury. This study also provides a modified procedure for separation and purification of Dityr, the main oxidized product in O-Tyr.