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

Abstract

After sciatectomy of the left hind-limb of C57BL/J mice, a denervation-induced muscular atrophy ensued and was accompanied by a decrease in the specific activity of glycogen phosphorylase to approx. 25 % of control values. The cofactor of phosphorylase, pyridoxal 5'-phosphate, was used as a specific label in the determination of the degradation rate of the enzyme following nerve section. After a delay of 3-4 days, phosphorylase was degraded approx. twice as rapidly in the denervated gastrocnemius (0.20 day-') as in the control muscle (0.12 day-'). The effect of denervation on phosphorylase mRNA was measured by quantitative Northern-blot analysis using a rat skeletal-muscle phosphorylase cDNA probe. After an initial rapid decline, phosphorylase mRNA levels stabilized in denervated muscle at 50 % of the value measured in the contralateral control muscle.

Role of the sarcoplasmic reticulum in regulating the activity-dependent expression of the glycogen phosphorylase gene in contractile skeletal muscle cells

“…Inhibition of contractile activity with either botulinum A toxin (BTX) or tetrodotoxin (TTX) reduced MGP mRNA levels to 30% of control levels after 7 days (Gorin et al, 1996;Mathews et al, 1998). This reduction is comparable to that observed 7 days after denervation, and the decrease in MGP mRNA levels precedes the reduction in protein levels (Leyland et al, 1990). BTX and TTX are highly selective neurotoxins that inhibit neuromuscular activity by different mechanisms.…”

“…and ␣AChR (Table 1) Persistent inhibition of neuromuscular activity is associated with increased sarcolemmal Na ϩ influx, sustained depolarization, and is followed by a reduction in steady-state transcript levels of glycolytic and glyco- genolytic enzymes (Leyland et al, 1990;Mathews et al, 1998). Increased Na ϩ influx can be associated with increased cytosolic-free Ca 2ϩ levels (Leader et al, 1984;Sreter et al, 1987).…”

Id-1 as a possible transcriptional mediator of muscle disuse atrophy.

“…Supersensitivity involves an increase in transcription, probably of all five acetylcholine receptor subunit genes (a, f3, y, 8, and E) (34). On the other hand, disuse decreases transcription of several other identified genese.g., a-actin (35,36), cytochrome c (35), aB-crystallin (37), and glycogen phosphorylase (38). In fact, disuse seems to induce a complex response involving up-and downregulation of a large number of genes (39).…”

Transgene‐coded chimeric proteins as reporters of intracellular proteolysis: Starvation‐induced catabolism of a lacZ fusion protein in muscle cells of Caenorhabditis elegans

“…Although some studies of muscle proteolysis have focused on well-defined substrates, (such as muscle glycogen phosphorylase) [Leyland et al, 1990], myosin heavy chains [Jakubiec-Puka et al, 1990], and acetylcholine receptor [Salpeter and Loring, 1985;Shyng et al, 1991;Shyng and Salpeter, 1990;Retzler et al, 1991;Caroni et al, 1993], proteolysis is often measured by release of labeled amino acids from total cellular protein. Biochemical analysis would be more straightforward if a more defined substrate were examined.…”