Effects of dietary oxidized tyrosine products on insulin secretion <i>via</i> the thyroid hormone T3-regulated TRβ1–Akt–mTOR pathway in the pancreas

Ding, Yin‐Yi; Tang, Xue; Cheng, Xiang‐Rong; Wang, Fangfang; Li, Zhu-Qing; Wu, Sha-Ji; Kou, Xingran; Shi, Yonghui

doi:10.1039/c7ra10435a

Cited by 13 publications

(14 citation statements)

References 73 publications

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“…Dityrosine was found to be responsible for the suppression of the T3 function in upregulating insulin synthesis‐related genes ( Ins2 , MafA , Pdx1 ). A further study (Ding, Tang et al., ) corroborated the lack of sensitivity of pancreatic islets to T3 after 12 weeks of dietary administration of oxidized tyrosine and dityrosine (8 g/kg diet). The authors proposed that both dityrosine and T3 may compete for the binding domain of TR β 1 receptors in pancreatic cells, disturbing the T3‐activated translation factors involved in the Akt–mTOR signaling pathway.…”

Section: Pathogenesis Of Dietary Protein Oxidation: Recent Advancesmentioning

confidence: 77%

Intake of Oxidized Proteins and Amino Acids and Causative Oxidative Stress and Disease: Recent Scientific Evidences and Hypotheses

Estévez

Xiong

2019

Journal of Food Science

116

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The exposure to reactive oxygen species (ROS) is an inevitable consequence of living in an aerobic world. The species contribute to the occurrence of oxidative stress in humans in which an uncontrolled production of ROS exceeds the endogenous antioxidant defences leading to the oxidative damage to essential cellular components, such as lipids, proteins, and DNA. The influence of diet on the modulation of the systemic redox status is recognized and, while some dietary components are found to be protective (that is, fruits and vegetables), others are recognized as pro‐oxidants (that is, processed meat and other animal‐source protein foods). Oxidized proteins and amino acids are potential promoters of luminal and postprandial oxidative stress; preliminary studies have actually reported noxious effects of these species in cultured cells and in experimental animals. However, the underlying pathological mechanisms remain poorly understood. The application of advanced methodological approaches based on mass spectrometric technologies and OMICS disciplines has enabled the elucidation of the molecular basis of the pathological effects of dietary oxidized proteins and amino acids. The present review collects the most recent evidences of the health risks of dietary protein oxidation and proposes reasonable hypotheses and future perspectives on the field.

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Section: Pathogenesis Of Dietary Protein Oxidation: Recent Advancesmentioning

confidence: 77%

Intake of Oxidized Proteins and Amino Acids and Causative Oxidative Stress and Disease: Recent Scientific Evidences and Hypotheses

Estévez

Xiong

2019

Journal of Food Science

116

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“…After ingestion, they can be absorbed into the blood circulation through the intestine and accumulate in the liver, kidney, pancreas, and brain . A study found that long-term feeding of OTP in mice can trigger pancreatic oxidative stress and induce liver and kidney fibrosis, and learning and memory dysfunction . Metabolomics analysis showed that the administration of 320 μg/kg DT solution for 6 weeks significantly reduced plasma 3-hydroxybutyrate and albumin levels, increased the content of trimethylamine oxide in plasma and urine, inhibited fatty acid metabolism and protein synthesis, and increased the risk of cardiovascular disease .…”

Section: Discussionmentioning

confidence: 99%

“…After T3 enters into cardiomyocytes, it binds to the thyroid hormone receptor and retinoic acid X receptor (RXRα) and coactivators, such as steroid receptor coactivator (Src-1), to regulate the expression of multiple target genes . Ding et al found that Dityr has a structure similar to T3, which can competitively bind to the pancreatic T3 receptor and inhibit the physiological effects of T3, resulting in insufficient ATP production and decreased insulin secretion in pancreatic cells . BPA and PCBs as structural analogs of T3 cause endocrine disorders and disrupt T3 action during development .…”

Section: Discussionmentioning

confidence: 99%

Dietary Dityrosine Induces Mitochondrial Dysfunction by Diminished Thyroid Hormone Function in Mouse Myocardia

Tang

et al. 2020

J. Agric. Food Chem.

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Oxidized tyrosine products (OTP) have been detected in commercial foods with high protein content, such as meat and milk products. OTP intake induces tissue oxidative stress and affects the normal activity of the hypothalamic−pituitary−thyroid axis (HPT). This study aims to investigate the effects of OTP and their main product, dityrosine (Dityr), on mouse myocardial function and myocardial energy metabolism. Mice received daily intragastric administration of either tyrosine (Tyr; 420 μg/kg body weight), Dityr (420 μg/kg body weight), or OTP (1909 μg/kg body weight) for 35 days. Additionally, H9c2 cells were incubated with various concentrations of Dityr for 72 h. We found that OTP and pure Dityr induced oxidative stress in growing mice and in H9c2 cells, resulting in a redox state imbalance, myocardial injury, mitochondrial dysfunction, and energy metabolism disorder. Dityr interferes with T3 regulation of the myocardium via the PI3K/AKT/GSK3β pathway, leading to myocardial mitochondrial damage and energy metabolism disorders. Food-borne OTP, especially Dityr, can disrupt thyroid hormone function in mouse myocardia leading to mitochondrial dysfunction, energy metabolism disorder, and oxidative stress.

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“…The presence of di-Tyr in foods, and consequent dietary intake, has resulted in studies on its toxicological properties. Intragastric administration of pure di-Tyr has been associated with metabolic alterations [ 151 ], including disrupted glucose metabolism [ 152 ], and renal alterations [ 153 ]. Interestingly, and of potential biological relevance, processed milks containing di-Tyr (and other Tyr oxidation products) can induce oxidative damage in plasma, liver and brain tissues, as well as spatial learning and memory impairments [ 154 ].…”

Section: Types Of Crosslinks Detected Within and Between Proteins And Peptidesmentioning

confidence: 99%

Oxidative Crosslinking of Peptides and Proteins: Mechanisms of Formation, Detection, Characterization and Quantification

et al. 2021

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Covalent crosslinks within or between proteins play a key role in determining the structure and function of proteins. Some of these are formed intentionally by either enzymatic or molecular reactions and are critical to normal physiological function. Others are generated as a consequence of exposure to oxidants (radicals, excited states or two-electron species) and other endogenous or external stimuli, or as a result of the actions of a number of enzymes (e.g., oxidases and peroxidases). Increasing evidence indicates that the accumulation of unwanted crosslinks, as is seen in ageing and multiple pathologies, has adverse effects on biological function. In this article, we review the spectrum of crosslinks, both reducible and non-reducible, currently known to be formed on proteins; the mechanisms of their formation; and experimental approaches to the detection, identification and characterization of these species.

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Effects of dietary oxidized tyrosine products on insulin secretion via the thyroid hormone T3-regulated TRβ1–Akt–mTOR pathway in the pancreas

Abstract: Oxidized tyrosine products (OTPs) have been detected in commercial foods with high protein content.

Cited by 13 publications

References 73 publications

Intake of Oxidized Proteins and Amino Acids and Causative Oxidative Stress and Disease: Recent Scientific Evidences and Hypotheses

Intake of Oxidized Proteins and Amino Acids and Causative Oxidative Stress and Disease: Recent Scientific Evidences and Hypotheses

Dietary Dityrosine Induces Mitochondrial Dysfunction by Diminished Thyroid Hormone Function in Mouse Myocardia

Oxidative Crosslinking of Peptides and Proteins: Mechanisms of Formation, Detection, Characterization and Quantification

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