Polypeptide derived from the ryanodine receptor that inhibits calcium leakage

Abstract

A polypeptide exhibiting the effect of inhibiting Ca 2+ leakage in a target cell, the polypeptide having the amino acid sequence of any of SEQ ID NOs: 3 to 9 or an amino acid sequence obtained through deletion, insertion, substitution, or addition of one or more amino acids in the aforementioned amino acid sequence; a polynucleotide encoding the polypeptide; and a pharmaceutical composition containing, as an active ingredient, the polypeptide or an expression product of the polynucleotide.

1 . A purified polynucleotide selected from the group consisting of:
 (a) a polynucleotide encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO: 3;   (b) a polynucleotide consisting of the DNA sequence of SEQ ID NO: 20 or a complementary strand thereof;   (c) a polynucleotide which can be hybridized with the polynucleotide described in (b) above under stringent conditions, wherein the hydridization is performed in 0.2×SSC containing 0.1% SDS at 50° C., followed by washing in 1×SSC containing 0.1% SDS at 60° C. and which can produce a corresponding expression product; and   (d) a polynucleotide which has a DNA sequence 80% or more homologous to the polynucleotide described in (a) above, and which can produce a corresponding expression product, an expression product of the polynucleotide exhibiting the effect of inhibiting Ca 2+  leakage in a target cell.   
     
     
         2 . A vector comprising the polynucleotide according to  claim 1 . 
     
     
         3 . A host cell comprising the vector according to  claim 2 . 
     
     
         4 . An expression product which is transformed with the host cell according to  claim 3 . 
     
     
         5 . A method of producing an expression product comprising
 transforming a host cell with a vector comprising a polynucleotide according to  claim 1  and   recovering said expression product.   
     
     
         6 . A pharmaceutical composition comprising, as an active ingredient, the expression product according  claim 4 . 
     
     
         7 . The pharmaceutical composition according to  claim 6 , which is administered to a target cell selected from the group consisting of human myocardial cell, smooth muscle cell, skeletal muscle cell, brain neuron, neuroblast, and pancreatic β cell. 
     
     
         8 . The pharmaceutical composition according to  claim 6 , which is a therapeutic agent for a disease selected from the group consisting of heart failure, cardiomyopathy, valvulopathy, ischemic heart disease, myocardial infarction, angina pectoris, arrhythmia, hypertension, peripheral circulatory disorder, diabetes, dysmnesia, cerebral infarction, and malignant hyperthermia. 
     
     
         9 . A method of producing a polypeptide consisting of the amino acid sequence of SEQ ID NO: 3 said method comprising:
 transforming a host cell with a vector comprising polynucleotide encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO: 3;   expressing said polypeptide; and   recovering said polypeptide from said host cell.