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Application of inner mitochondrial membrane transport protein 50 (TIM50) in treating myocardial hypertrophy

A transport protein and cardiac hypertrophy technology, applied in the field of gene function and application, can solve problems such as adverse consequences, neurodevelopmental disorders, and unexplained functional relationships, etc., to protect cardiac function, resist cardiac fibrosis, cardiac hypertrophy, inhibit The effect of cardiac hypertrophy

Active Publication Date: 2015-12-30
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Inhibiting the expression of TIM50 in zebrafish can lead to neurodevelopmental disorders, muscle fiber shortening, and disordered arrangement[21], and the mechanism may affect mitochondrial membrane permeability, resulting in changes in mitochondrial protein components, thereby affecting mitochondrial function, and ultimately leading to series of adverse consequences
In 2012, MelanieR.Duncan et al. found that TIM50 can inhibit the activity of voltage-dependent anion channels on mitochondria through its phosphatase activity[22], but did not clearly explain its relationship with mitochondria or cell function

Method used

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  • Application of inner mitochondrial membrane transport protein 50 (TIM50) in treating myocardial hypertrophy
  • Application of inner mitochondrial membrane transport protein 50 (TIM50) in treating myocardial hypertrophy
  • Application of inner mitochondrial membrane transport protein 50 (TIM50) in treating myocardial hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] [Example 1] Expression of TIM50 in the hearts of normal people and patients with cardiomyopathy

[0082]SDS-PAGE-immunoblotting test (Westernblot) was performed on proteins extracted from the hearts of normal human hearts (individuals donated by non-cardiac causes of death) and hearts of patients with dilated cardiomyopathy (recipients replaced by patients undergoing heart transplantation, DCM). , combined with antibodies that specifically recognize TIM50 protein and cardiomyocyte hypertrophy markers ANP (Millipore, AB2232) and β-MHC (santacruz, sc53090) to detect the expression of TIM50 (santacruz, sc55338), GAPDH (CellSignalingTechnology, 2128) Do internal reference. Test results such as figure 1 As shown, the expression of cardiomyocyte hypertrophy markers ANP and β-MHC in the hearts of patients with dilated cardiomyopathy was significantly up-regulated, and the expression of TIM50 was significantly down-regulated ( figure 1 );

Embodiment 2

[0083] [Example 2] Expression of TIM50 in wild-type mouse Sham group and AB operation group 4W, 8W heart

[0084] 1. The myocardial hypertrophy model adopts aortic arch coarctation surgery, and the operation process of the model is as follows:

[0085] 1.1 Preoperative preparation

[0086] (1) Anesthesia: First weigh the mice, calculate the required amount of anesthetic (3% pentobarbital sodium) according to 90 mg / kg body weight, inject intraperitoneally, and record the injection time point. There is no obvious reaction between tail and toe pinching and the mouse is in good condition. This is the standard for successful anesthesia (generally there is no obvious reaction about 10 minutes after injection, and the mouse has a reaction to pinch toe about 50 minutes after anesthesia, and about 30 minutes after anesthesia is the best operation time).

[0087] (2) Preparation of the operation area: the skin of the left chest, left chest and armpit of the left forelimb of the mouse w...

Embodiment 3

[0097] [Example 3] Expression of TIM50 in cardiomyocytes stimulated by control group (PBS) or angiotensin II (AngII) or phenylephrine (PE)

[0098] Isolate and culture newborn 1-day Sprague-Dawley neonatal rat cardiomyocytes, culture the primary cardiomyocytes for 48 hours, change the medium, add serum-free DMEM / F12 starved cardiomyocytes for 12 hours to synchronize the cells, and give PBS and angiotensin II (AngII respectively) , 1 μM), phenylephrine (PE, 1 μM) stimulation for 48 hours, SDS-PAGE-immunoblotting test (Western blot) was performed on the protein extracted from cardiomyocytes, combined with specific recognition of TIM50 protein and cardiomyocyte hypertrophy markers ANP, β-MHC The antibody was detected, and the expression of TIM50 was determined, and the detection results were as follows: image 3 shown. Such as image 3 As shown, the expressions of ANP and β-MHC in cardiomyocytes stimulated by angiotensin II (AngII) or phenylephrine (PE) were significantly up-re...

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Abstract

The invention discloses application of inner mitochondrial membrane transport protein 50 in protecting heart function, resisting cardiac fibrosis and / or preventing and relieving and / or treating myocardial hypertrophy and belongs to the field of gene application. The circumstance that expression of TIM50 in a model occurring myocardial hypertrophy is remarkably lowered when compared with that of a normal group is determined; inhibition of TIM50 expression remarkably promotes myocardial hypertrophy and fibrosis and deteriorates the heart function while promotion of TIM50 overexpression remarkably inhibits myocardial hypertrophy and fibrosis and protects the heart function. The TIM50 can serve as a drug target to be used for screening drug for protecting heart function, resisting cardiac fibrosis and / or preventing and relieving and / or treating myocardial hypertrophy; the TIM50 can serve as a target gene in gene treatment to be used for designing and preparing drug and / or biological preparations for protecting heart function, resisting cardiac fibrosis and / or preventing and relieving and / or treating myocardial hypertrophy, and a novel effective approach is provided for treatment of myocardial hypertrophy.

Description

technical field [0001] The invention belongs to the field of gene function and application, in particular to the function and application of a mitochondrial inner membrane transporter 50 (TIM50) in the treatment of cardiac hypertrophy, specifically the application in the preparation of drugs for the prevention, alleviation and / or treatment of cardiac hypertrophy . Background technique [0002] Hypertrophic cardiomyopathy (HCM) is a compensatory response of the myocardium to long-term biomechanical pressure or increased volume load. It is common in cardiovascular diseases such as hypertension and aortic valve stenosis. Increased, extracellular matrix and other characteristics [1-3]. Hypertension and senile degenerative aortic valve disease are on the rise year by year in our country. Cardiac hypertrophy and the incidence of hypertension and heart disease caused by hypertension and other diseases also increase thereupon. Although myocardial hypertrophy can initially increas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K48/00A61P9/00G01N33/68
Inventor 李红良徐亚伟赵逸凡王丕晓张晓晶
Owner WUHAN UNIV
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