Accelerated degradation of glycogen phosphorylase in denervated and dystrophic mouse skeletal muscle

Abstract

Pyridoxal phosphate, the cofactor of glycogen phosphorylase, fulfils the criteria needed of a turnover label for this enzyme. The decay of protein-bound label following administration of [3H]pyridoxine is a good index of the rate of degradation of the enzyme in vivo. This method has been applied to the study of catabolism of the enzyme in normal, denervated and dystrophic mouse skeletal muscle. In both of the pathological conditions the enzyme is degraded more rapidly than normal.

Effect of denervation on the expression of glycogen phosphorylase in mouse skeletal muscle

“…These values are in close agreement with those found by Butler et al (1985a), who obtained a rate constant of 0.198 day-1 (t1 = 3.5 days) for phosphorylase in the denervated gastrocnemius and 0.1 16 day-' (t, = 6.0 days) in the contralateral control between 14 and 28 days after nerve section. In contrast with the previous study, which examined the turnover of phosphorylase in a new and denervated steady state, we have determined the rate of degradation as phosphorylase moves towards the new steady state.…”

“…The increased rate of catabolism of phosphorylase occurs in the denervated muscle after about 3-4 days of denervation. Moreover, this increased rate is maintained for at least 4 weeks (Butler et al, 1985a).…”

“…The intracellular concentration of the enzyme declines in response to denervation in mice (Butler et al, 1985a), chickens (Shackleford & Lebherz, 1981) and rats (Lawrence & Smith, 1990). However, it is not clear whether the decay in phosphorylase levels is elicited via changes in the rate of synthesis and/or degradation of the enzyme.…”

“…Denervation of skeletal muscle results in a marked decrease in phosphorylase levels (Turner & Manchester, 1972;Butler et al, 1985a). In denervated chick breast muscle the levels of several glycolytic enzymes, including phosphorylase, decreased by 50 % compared with the innervated control; this new steady state was established within 2 weeks of nerve section (Shackleford & Lebherz, 1981).…”

“…The rate of degradation of phosphorylase was measured as the rate of clearance of total phosphorylase-bound radioactivity (Butler et al, 1985a Beynon, 1989). Fig.…”