ABSTRACT
Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO=0.60±0.11, control=1.07±0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-β1 (rhEPO=0.95±0.14, control=1.05±0.16) and TNF-α (rhEPO=0.73±0.20, control=1.01±0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.
Subject(s)
Animals , Male , Down-Regulation/drug effects , Erythropoietin/therapeutic use , Gene Expression/drug effects , Muscular Dystrophy, Duchenne/drug therapy , Myostatin/metabolism , Recombinant Proteins/therapeutic use , Disease Models, Animal , Dystrophin/deficiency , Mice, Inbred mdx , Muscle Strength/drug effects , Muscle, Skeletal/metabolism , Muscular Dystrophy, Duchenne/metabolism , Myostatin/genetics , Phenotype , Real-Time Polymerase Chain Reaction , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-ß1 (TGF-ß1), and tumor necrosis factor-α (TNF-α) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO = 0.60 ± 0.11, control = 1.07 ± 0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-ß1 (rhEPO = 0.95 ± 0.14, control = 1.05 ± 0.16) and TNF-α (rhEPO = 0.73 ± 0.20, control = 1.01 ± 0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.
Subject(s)
Down-Regulation/drug effects , Erythropoietin/therapeutic use , Gene Expression/drug effects , Muscular Dystrophy, Duchenne/drug therapy , Myostatin/metabolism , Recombinant Proteins/therapeutic use , Animals , Disease Models, Animal , Dystrophin/deficiency , Male , Mice, Inbred mdx , Muscle Strength/drug effects , Muscle, Skeletal/metabolism , Muscular Dystrophy, Duchenne/metabolism , Myostatin/genetics , Phenotype , Real-Time Polymerase Chain Reaction , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The synthesis of a series of novel 1-[(benzofuran-2-yl)phenylmethyl]-triazoles and -tetrazoles is described. The compounds were tested for human placental aromatase inhibition in vitro, using [1beta-3H]-androstenedione as the substrate for the aromatase enzyme, the percentage inhibition and IC50 data is included.
