Leucine suppresses acid-induced protein wasting in L6 rat muscle cells.
BACKGROUND
Metabolic acidosis induces protein wasting in skeletal muscle cells, accompanied by decreased glycolysis and compensatory increased consumption of other metabolic fuels, implying that protein wasting arises from fuel starvation and might be rectified by fuel supplements. Design To test this hypothesis, total protein and protein degradation (release of 14C-phenylalanine) were measured in L6 skeletal muscle cells cultured in Eagle's Minimum Essential Medium at pH 7.1-7.5 for 3 days with metabolic inhibitors or metabolic fuel supplements.


RESULTS
Inducing metabolic fuel starvation with inhibitors (1 mmol L(-1) 2-deoxyglucose or 0.1 mmol L(-1) KCN [potassium cyanide]) failed to stimulate protein degradation or net protein wasting under nonacidaemic conditions (pH 7.5). Conversely metabolic fuel supplements (1 mmol L(-1) octanoate, pyruvate or alanine) failed to increase the protein content of the cultures at any pH tested, in spite of significant consumption of the fuels by the cells. Only leucine (1-3 mmol L(-1)) increased protein content and suppressed protein degradation in opposition to the catabolic effect of acidaemia (pH 7.1). Conclusion Leucine exerts a beneficial anabolic effect on cultured skeletal muscle cells in the face of metabolic acidaemia. The failure of other metabolic fuels to do this, and of the metabolic inhibitors to exert a catabolic effect, suggests that leucine acts as a specific modulator of protein turnover and not as a nonspecific source of carbon for oxidation as a fuel.
Bevington
A
A
Department of Nephrology, Leicester General Hospital, Leicester, UK. ab74@leicester.ac.uk
Brown
J
J
Walls
J
J
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D002460:Cell Line; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D007930:Leucine / Q000494:pharmacology*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D019282:Wasting Syndrome / Q000378:metabolism / Q000517:prevention & control
D002210:Caprylates; D005230:Fatty Acids, Nonesterified; D009124:Muscle Proteins; D007930:Leucine; C031492:octanoic acid