Muscular atrophy-inducing agent using hypometabolism-inducing substance t1am, and use thereof in treating muscular hypertrophy

Abstract

A screening method for a drug for treating muscular atrophy is proposed. The method may include the steps of: (a) inducing muscular atrophy by administering to a normal cell or a normal animal a hypometabolism-inducing substance selected from the group consisting of 3-iodothyronamine (T1AM), [D-Ala2, D-Leu5] enkephalin (DADLE), 5′-adenosine monophosphate (5′-AMP), and hydrogen sulfide (H2S); (b) treating a candidate substance in the cell or animal treated with the hypometabolism-inducing substance; (c) evaluating the degree of improvement or treatment of muscular atrophy in the cell or animal treated with the candidate substance; and (d) determining the candidate substance as a drug for treating muscular atrophy.

What is claimed is: 
     
         1 . A screening method for a drug for treating muscular atrophy, comprising:
 (a) inducing muscular atrophy by administering to a normal cell or a normal animal a hypometabolism-inducing substance selected from the group consisting of 3-iodothyronamine (T1AM), [D-Ala2, D-Leu5] enkephalin (DADLE), 5′-adenosine monophosphate (5′-AMP), and hydrogen sulfide (H 2 S);   (b) treating a candidate substance in the cell or animal treated with the hypometabolism-inducing substance;   (c) evaluating the degree of improvement or treatment of muscular atrophy in the cell or animal treated with the candidate substance; and   (d) determining the candidate substance as a drug for treating muscular atrophy.   
     
     
         2 . The screening method of  claim 1 , wherein in step (d), as compared to a control treated with DMSO, physiological saline, sterilized distilled water, carboxymethyl cellulose or phosphate buffered saline (PBS), when the group treated with the candidate substance has at least one result selected from the group consisting of:
 an increase in size of myotubes or size of muscle;   a decrease in expression ratio of p-AMPK/AMPK;   an increase in expression ratio of p-Akt1/Akt1;   an increase in expression ratio of p-S6K/S6K;   an increase in expression ratio of p-FoxO1/FoxO1;   an increase in expression ratio of p-FoxO3/FoxO3;   a decrease in expression level of MuRF1;   a decrease in activity of proteasome;   an increase in expression level of heat shock protein 72 (HSP72); and   an increase in expression level of αB-crystallin, the candidate substance is determined as the drug for treating muscular atrophy.   
     
     
         3 . The screening method of  claim 1 , wherein the hypometabolism-inducing substance in step(a) is 3-iodothyronamine (T1AM). 
     
     
         4 . The screening method of  claim 3 , wherein a dose of the 3-iodothyronamine (T1AM) is 0.1 μM to 1000 μM in the case of the cell, and 10 to 500 mg/kg per unit weigh (kg) of the animal in the case of the animal. 
     
     
         5 . The screening method of  claim 1 , wherein the administering of the hypometabolism-inducing substance is performed by a method selected from the group consisting of oral administration, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, and intradermal administration. 
     
     
         6 . The screening method of  claim 1 , wherein the cell is a muscle cell and, the animal is a vertebrate.