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Application of succinylation-related preparations for regulation of mitochondrion OCR

A succinylation, mitochondrial technology, applied in the biological field, can solve problems such as unclear effect

Pending Publication Date: 2019-11-05
SHANDONG PROVINCIAL HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, the role of lysine succinylation in thyroid disease is unclear and needs further study

Method used

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  • Application of succinylation-related preparations for regulation of mitochondrion OCR
  • Application of succinylation-related preparations for regulation of mitochondrion OCR
  • Application of succinylation-related preparations for regulation of mitochondrion OCR

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1, Animal Model-Construction of Rat Thyroid Dysfunction Model Induced by High Fat Diet

[0051] Twenty-six male SD rats (Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.), weighing 190-210 g, were placed under constant temperature and humidity conditions and subjected to a 12h:12h light-dark cycle. Rats were randomly divided into two groups: CD control group (n=13, carried out common diet) and HFD research group (n=13, carried out high-fat diet), the detailed composition of fatty acids in the diet is shown in Table 1, weighed every week Rats were reweighted and fed for 24 weeks to establish a model of thyroid dysfunction induced by a high-fat diet. Our previous study found that excessive intake of dietary fat caused significant thyroid dysfunction and hypothyroidism in rats, see "S.S. Shao, Y.F. Zhao, Y.F. Song, C. Xu, J.M. Yang, S.M. Xuan, H.L. Yan , C.X.Yu, M.Zhao, J.Xu, J.J.Zhao, Acta Pharmacol Sin 2014,35,1411" and literature "X.Zhang, W.Chen,...

Embodiment 2

[0056] Example 2. General Characteristics of Quantitative Proteome in Thyroid Tissue of Animal Model

[0057] The rat thyroid tissues of the CD control group and the HFD research group preserved in Example 1 were taken, and protein extraction and trypsin digestion were performed respectively to obtain peptides, and then the peptides were fractionated by high-performance liquid chromatography (HPLC) and high-resolution liquid chromatography. Quantitative proteome-wide analysis was performed by phase chromatography-mass spectrometry (LC-MS / MS).

[0058] Results A total of 3869 proteins were identified, 2982 of which were quantitatively changed between the two groups of rats. Taking the change of the fold value of the difference (HFD study group relative to the CD control group) more than 1.5 times as a significant up-regulation, and less than 1 / 1.5 as a significant down-regulation change standard, the two groups of rats expressed a total of 129 differentially expressed proteins,...

Embodiment 3

[0082] Example 3. Enrichment Analysis of Differentially Expressed Proteins in Thyroid Tissues of Animal Models

[0083] According to the annotation of all proteins identified in Example 2 and the screening of differentially expressed proteins, we carried out enrichment analysis of functional annotation types such as GO, KEGG, and protein domains, with the purpose of detecting whether differentially expressed proteins are in certain functional types There is a significant enrichment trend. Negative logarithmic (-log10) transformation was performed on the p value obtained by the enrichment test (Fisher's exact test was used here), that is, the larger the converted value, the more significant the enrichment of this functional type.

[0084] Classify the biological processes and molecular functions of differentially expressed proteins through GO functional annotation analysis, such as Figure 5 and Figure 6 As shown, in cellular components, the expression of proteins localized ...

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Abstract

The invention discloses application of succinylation-related preparations for the regulation of mitochondrion OCR. According to the application of the succinylation-related preparations for the regulation of the mitochondrion OCR, mitochondrion oxygen consumption (p<average>is less than 0.05) is significantly reduced after treatment of human thyroid epithelial cells with palmitic acid, while the change of the mitochondrion oxygen consumption(p<average>is less than 0.05) is on the contrary after treatment of the human thyroid epithelial cells with palmitic acid and a desuccinylation inhibitor.The result of further detection of succinylation IDH2 (isocitrate dehydrogenase 2) shows that the result is achieved by regulating the succinylation of IDH2, that is, the succinylation of the IDH2 isreduced, mitochondrion OCR is reduced, and the desuccinylation inhibitor is involved in increasing or restoring succinylation of the IDH2, and the mitochondrion OCR is enabled to be increased or restored. The application of the succinylation-related preparations for the regulation of the mitochondria OCR provides a novel drug target for the treatment of congenital hypothyroidism.

Description

technical field [0001] The invention relates to the field of biotechnology, and relates to the application of succinylation-related preparations in regulating mitochondrial OCR, in particular to the use of desuccinylation inhibitors in improving mitochondrial OCR disorders. Background technique [0002] Thyroid hormones are synthesized and secreted by the thyroid gland and play a vital role in normal human development, differentiation and metabolism. Disorders of thyroid hormones can lead to a variety of thyroid diseases. [0003] Hypothyroidism is a common and serious disorder of the endocrine system. Thyroxine deficiency refers to low serum total thyroxine (TT4), which often leads to elevated thyroid-stimulating hormone (TSH) concentrations through negative feedback on the hypothalamus-pituitary-thyroid axis. Primary hypothyroidism is caused by the dysfunction of the thyroid gland itself and is the main cause of hypothyroidism. The onset of hypothyroidism in adults is o...

Claims

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Application Information

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IPC IPC(8): A61K31/4406A61K31/165A61P5/14
CPCA61K31/4406A61K31/165A61P5/14
Inventor 赵家军赵萌高聆邵珊珊胡宝祥
Owner SHANDONG PROVINCIAL HOSPITAL
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