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Title: GLUTAMINE PREVENTS DOWN-REGULATION OF MYOSIN HEAVY CHAIN SYNTHESIS AND MUSCLE ATROPHY FROM GLUCOCORTICOIDS

Author
item HICKSON R C - UNIV ILLINOIS AT CHICAGO
item Czerwinski, Susan
item WEGRZYN L E - UNIV ILLINOIS AT CHICAGO

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: The aims of this study were to determine whether glutamine infusion prevents the decline in protein synthesis and muscle wasting associated with repeated glucocorticoid treatment. Hormone (cortisol acetate, 100 mg-kg bw-l-day-l) and vehicle- (carboxymethyl cellulose) treated female rats were infused with either saline or glutamine (240 mM, 0.75 ml/hr) for a seven-day period. Glutamine infusion attenuated the decline of plantaris muscle glutamine concentration (3.0 vs. 2.3 umoles/g) and prevented over 70% of the total muscle mass losses due to the glucocorticoid injections. Fractional synthesis rates of myosin heavy chain (MHC) and total protein were determined following constant [3H] leucine infusion from the leucyl-tRNA precursor pool, which was similar in all groups (range 4.8 to 6.3 dpm/pmol). MHC synthesis rates (%/day) in plantaris muscles were reduced to 40% of controls (4.2/9.4). While glutamine had no effect on MHC synthesis in vehicle-treated animals (10.1/9.4), it prevented 50% (7.6/4.2) of the hormone-induced decline in MHC synthesis rates. The same results were obtained with total protein synthesis measurements. In conclusion, these data show that glutamine infusion is effective therapy in counteracting glucocorticoid-induced muscle atrophy. The mechanism of atrophy prevention appears related to maintaining muscle glutamine levels which, in turn, may limit the glucocorticoid down-regulation of MHC synthesis. The similarity of total protein and MHC synthesis results indicates that MHC effects are synchronized with the hormonal and glutamine effects on total protein metabolism.

Technical Abstract: The aims of this study were to determine whether glutamine infusion prevents the decline in protein synthesis and muscle wasting associated with repeated glucocorticoid treatment. Hormone (cortisol acetate, 100 mg-kg bw-l-day-l) and vehicle- (carboxymethyl cellulose) treated female rats were infused with either saline or glutamine (240 mM, 0.75 ml/hr) for a seven-day period. Glutamine infusion attenuated the decline of plantaris muscle glutamine concentration (3.0 vs. 2.3 umoles/g) and prevented over 70% of the total muscle mass losses due to the glucocorticoid injections. Fractional synthesis rates of myosin heavy chain (MHC) and total protein were determined following constant [3H] leucine infusion from the leucyl-tRNA precursor pool, which was similar in all groups (range 4.8 to 6.3 dpm/pmol). MHC synthesis rates (%/day) in plantaris muscles were reduced to 40% of controls (4.2/9.4). While glutamine had no effect on MHC synthesis in vehicle-treated animals (10.1/9.4), it prevented 50% (7.6/4.2) of the hormone-induced decline in MHC synthesis rates. The same results were obtained with total protein synthesis measurements. In conclusion, these data show that glutamine infusion is effective therapy in counteracting glucocorticoid-induced muscle atrophy. The mechanism of atrophy prevention appears related to maintaining muscle glutamine levels which, in turn, may limit the glucocorticoid down-regulation of MHC synthesis. The similarity of total protein and MHC synthesis results indicates that MHC effects are synchronized with the hormonal and glutamine effects on total protein metabolism.