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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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Abstract

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.

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Abbreviations

AOPPs:

Advanced oxidized protein products

BUN:

Blood urea nitrogen

CAT:

Catalase

Dityr:

Dityrosine

ECM:

Extracellular matrix

GPX:

Glutathione peroxidase

HE:

Hematoxylin-eosin

HA:

Hyaluronic acid

ICTP:

Procollagen type I carboxy terminal peptide

IL:

Interleukin

LN:

Laminin

LOX:

Lipid oxidation

MDA:

Malondialdehyde

OPPs:

Oxidized protein products

PIIINP:

Type III procollagen peptide

PC:

Protein carbonyl

P-JNK:

Phosphorylation of JNK

P-p38:

Phosphorylation of p38

POX:

Protein oxidation

ROS:

Reduced oxygen species

SOD:

Superoxide dismutase

SCr:

Serum creatinine

T-AOC:

Total antioxidant capacity

UV:

Urine volume

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Acknowledgments

We express our deepest gratitude to all those people whose kindness and advice have made this work possible. We especially thank Prof. Charles Shoemaker (University of California, Davis) for his effective advice and encouragement. We thank Dr. Xue Tang, Dr. Xiangrong Cheng and Dr. Biao Yan in our lab for their help in the experimental result analysis. We thank Dr. Hui Pan (Shanghai Jiao Tong University) for her continuing help of downloading references related to our study. We also thank Malik Muhammad Umair (School of Textile and Clothing, Jiangnan University) for the language help in this paper. This work is supported by the Open Project Program of State Key Laboratory of Food Science and Technology, Jiangnan University, China (No. SKLF-ZZB-201609), the National Natural Science Foundation of China (No. 30571347 and No. 31571841),and the Fundamental Research Funds for the Central Universities (JUSRP111A36).

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Authors and Affiliations

  1. The Laboratory of Food Nutrition and Functional Factors, Food Science and Technology, Jiangnan University, Wuxi, 214122, China

    Zhuqing Leslie Li, Yonghui Shi, Yinyi Ding, Yumei Ran & Guowei Le

  2. The State Key Laboratory of Food Science and Technology, Food Science and Technology, Jiangnan University, Wuxi, 214122, China

    Yonghui Shi & Guowei Le

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  1. Zhuqing Leslie Li
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Correspondence to Guowei Le.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Li, Z.L., Shi, Y., Ding, Y. et al. Dietary oxidized tyrosine (O-Tyr) stimulates TGF-β1-induced extracellular matrix production via the JNK/p38 signaling pathway in rat kidneys. Amino Acids 49, 241–260 (2017). https://doi.org/10.1007/s00726-016-2353-6

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