KR-102961601-B1 - Composition for preventing, ameliorating or treating disease caused by nitration of protein comprising peptide with tyrosine at the terminal as effective component

Abstract

The peptide of the present invention, having tyrosine located at the terminal end, has an excellent effect of inhibiting protein nitration and has an excellent effect of preventing, improving, or treating symptoms of disease in a chronic somatic confinement stress depression/cognitive impairment induction model, Alzheimer's dementia model, epileptic seizure model, stroke model, type 2 diabetes model, acute renal failure model, or hyperammonemia model.

Inventors

• 김현준
• 김영범
• 강재순
• 정순웅
• 송미영
• 백지형
• 박상원
• 김화진
• 유대영

Assignees

• 경상국립대학교산학협력단

Dates

Publication Date

20260507

Application Date

20220223

Priority Date

20210223

Claims (10)

1. A health functional food composition for the prevention or improvement of diseases caused by the nitration of a protein containing, as an active ingredient, a peptide having tyrosine located at the terminal end or a food-grade acceptable salt thereof, wherein i) A health functional food composition characterized in that the peptide is tyrosine-glutamine (YQ) or glutamine-tyrosine (QY), and the disease is a depressive disorder or an anxiety disorder; or ii) A health functional food composition characterized in that the above peptide is tyrosine-glutamine (YQ), and the above disease is a disease caused by the nitration of any one protein selected from stroke, epilepsy, seizure, cognitive impairment, Alzheimer's disease, dementia, acute kidney injury, hyperammonemia, and hepatic encephalopathy.
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5. A pharmaceutical composition for the prevention or treatment of diseases caused by the nitration of a protein, comprising as an active ingredient a peptide having tyrosine located at the terminal or a pharmaceutically acceptable salt thereof, wherein i) A pharmaceutical composition characterized in that the peptide is tyrosine-glutamine (YQ) or glutamine-tyrosine (QY), and the disease is a depressive disorder or an anxiety disorder; or ii) A pharmaceutical composition characterized in that the above peptide is tyrosine-glutamine (YQ), and the above disease is a disease caused by the nitration of any one protein selected from stroke, epilepsy, seizure, cognitive impairment, Alzheimer's disease, dementia, acute kidney injury, hyperammonemia, and hepatic encephalopathy.
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Description

Composition for preventing, ameliorating, or treating disease caused by nitration of protein comprising a peptide with tyrosine at the terminal as an effective component The present invention relates to a composition for the prevention, improvement, or treatment of diseases caused by the nitration of proteins, comprising a peptide having tyrosine located at the terminal end as an active ingredient. Oxidative stress is known to occur when oxygen generated during metabolic processes acts as free radicals, damaging cells and causing various diseases. In particular, proteins undergo nitration due to reactive oxygen species (ROS) or reactive nitrogen species (RNS) present within cells. This protein nitration is known as a byproduct accompanying the oxidation process; when specific proteins are nitrated, structural mutations lead to functional deterioration, resulting in various diseases. Protein nitration has been reported to be closely related to intracellular signaling, diseases caused by inflammatory responses, neurodegenerative diseases, and aging. More recently, it has also been reported to affect conditions such as asthma, diabetes, cancer, chronic stress-induced depression, type 2 diabetes, and acute renal disease. Therefore, research on protein nitration can play a crucial role in both biological and clinical aspects, and there is a pressing need for research on the development of substances that inhibit protein nitration. Meanwhile, Korean Registered Patent No. 1897400 discloses 'a composition for inhibiting the activity of tyrosine dicarboxylase and a method for manufacturing a fermented food using the same' and Korean Published Patent No. 2018-0021746 discloses 'a method for purifying an aromatic compound nitrated from a nitration process,' but there is no description of the present invention's 'composition for preventing, improving, or treating diseases caused by the nitration of a protein containing a peptide having tyrosine at the terminal end as an active ingredient.' Figure 1 shows the process of the object recognition test (ORT) and object location recognition test (OLT) conducted to analyze the long-term memory ability of animals according to the peptide diet of the present invention. Figure 2 confirms the protein nitration inhibitory effect of the peptide according to the present invention, where A is the Western blot result for nitrotyrosine protein in PFC (prefrontal cortex) tissue and B is the Western blot result for nitrotyrosine protein in liver tissue. Figure 3 is a Western blot result for insulin receptor beta and phosphorylated insulin receptor beta proteins in liver tissue to confirm the protein expression level regulating effect of the peptide according to the present invention. Figure 4 shows the results of confirming the inhibitory effect of peptides with tyrosine terminals on the nitration of Cu/ZnSOD (A) and MnSOD (B). PN is peroxynitrite, which induces protein nitration. * and *** indicate that the activity of Cu/ZnSOD or MnSOD in the peptide-treated group was statistically significantly increased compared to the PN-alone treated group, with * being p<0.05 and *** being p<0.001. Figure 5 shows the results of confirming the inhibitory effect of a peptide with a tyrosine terminal on the nitration of glutamine synthase. PN is peroxynitrite, which induces protein nitration. ** indicates that the activity of glutamine synthase in the peptide-treated group was statistically significantly increased compared to the PN-alone treated group, and p<0.01. Figure 6 is a Western blot result confirming the inhibitory effect of a peptide with tyrosine located at the terminal end on catalase nitration. Figure 7 shows the results of confirming the nitration inhibitory effect by measuring the refolding activity of HSP60 (Heat shock protein 60) by a peptide with tyrosine at the terminal end. RLU represents the difference in absorbance (relative light unit) measured at Time 0 and Time 60. Figure 8 shows the results of confirming GS activity (A), GS expression amount (B), and nitration levels of tyrosine contained in GS (C and D) according to the tyrosine-glutamine peptide diet (PD) in the chronic somatic confinement stress-induced group (STR). Figure 9 shows the results of confirming GS activity (A), GS expression amount (B), and nitration levels of tyrosine contained in GS (C and D) according to glutamine-tyrosine peptide diet (PD) in a chronic somatic confinement stress-induced group (STR). Figure 10 shows the results of confirming plasma corticosterone concentration (A), sucrose preference (B), plasma ROS/RNS concentration (C), and PFC tissue ROS/RNS concentration (D) according to the tyrosine-glutamine peptide diet (PD) in the chronic somatic confinement stress-induced group (STR). Figure 11 shows the results of confirming plasma corticosterone concentration (A), sucrose preference (B), plasma ROS/RNS concentration (C), and PFC tissue ROS/RNS concentration (D) according to the glutamine-tyrosine