Methods and products for manipulating uncoupling protein expression

Abstract

The invention is based in part on the discovery that uncoupling proteins (UCPs) are expressed in the plasma membrane of rapidly dividing cells but not of growth arrested, chemotherapy resistant cells. It has also been found according to the invention that UCP is expressed in the lysosomal membrane under certain metabolic conditions. Thus the invention is methods, products, screening assays and kits relating to the manipulation of UCP expression within cellular and intracellular membranes.

1 . A method for inhibiting plasma membrane UCP expression in a cell, comprising:
 contacting a cell with a plasma membrane UCP inhibitor to inhibit plasma membrane UCP expression, wherein the plasma membrane UCP inhibitor is selected from the group consisting of a UCP binding peptide or molecule, an anti-UCP antibody, a hydrophobic nucleotide analog, and a non-omega-3 fatty acid.   
     
     
         2 .- 37 . (canceled) 
     
     
         38 . A method for sensitizing a resistant tumor cell to a cytotoxic therapy, comprising:
 expressing a functional UCP or UCP fragment in a plasma membrane of a resistant tumor cell to sensitize the resistant tumor cell to a cytotoxic therapy.   
     
     
         39 . The method of  claim 38 , wherein the method is performed in a subject having a cancer. 
     
     
         40 .- 55 . (canceled) 
     
     
         56 . A method for inducing cellular division in a growth arrested cell, comprising: expressing a functional UCP or UCP fragment in a plasma membrane of a growth arrested cell to induce cell division of the cell. 
     
     
         57 . The method of  claim 56 , wherein the growth arrested cell is a nerve cell. 
     
     
         58 . The method of  claim 57 , wherein the functional UCP or UCP fragment is administered to a subject in conjunction with a delivery vehicle. 
     
     
         59 . The method of  claim 58 , wherein the delivery vehicle is a liposome. 
     
     
         60 . A method for regulating lysosomal pH, comprising:
 modifying lysosomal UCP activity in a cell to regulate lysosomal pH.   
     
     
         61 .- 62 . (canceled) 
     
     
         63 . The method of  claim 60 , wherein the lysosomal UCP activity is modified by contacting the cell with a lysosomal UCP inhibitor. 
     
     
         64 . The method of  claim 63 , wherein the lysosomal UCP inhibitor is selected from the group consisting of a dominant negative lysosomal UCP, and a lysosomal targeted binding peptide or molecule. 
     
     
         65 . The method of  claim 60 , wherein the lysosomal UCP activity is modified by contacting the cell with a lysosomal UCP activator. 
     
     
         66 . A method for treating or preventing an infectious disease, comprising:
 administering to a subject having or at risk of developing an infectious disease a lysosomal UCP inhibitor in an effective amount for treating or preventing the infectious disease.   
     
     
         67 . The method of  claim 66 , wherein the lysosomal UCP inhibitor is selected from the group consisting of a dominant negative lysosomal UCP, and a lysosomal targeted binding peptide or molecule. 
     
     
         68 . The method of  claim 66 , further comprising administering an antigen to the subject. 
     
     
         69 . The method of  claim 68 , wherein the antigen is selected from the group consisting of a viral, a bacterial, a parasitic, and a fungal antigen. 
     
     
         70 . The method of  claim 66 , wherein the subject is infected with an intracellular pathogen. 
     
     
         71 . The method of  claim 70 , wherein the intracellular pathogen is an intracellular bacteria. 
     
     
         72 . The method of  claim 70 , wherein the intracellular pathogen is an intracellular parasite. 
     
     
         73 . A method for treating autoimmune disease, comprising:
 administering to a subject having autoimmune disease a UCP activator in an effective amount to prevent antigen presentation.   
     
     
         74 . The method of  claim 73 , wherein the UCP activator is a functional UCP or UCP fragment with a lysosomal membrane targeting molecule.