Abnormal Polyamine Metabolism in Hereditary Muscular Dystrophies

Abstract

A B S T R A C T Previous studies showed hyperresponsiveness to human growth hormone (hGH) in men with myotonic or limb girdle dystrophies (MMD or LGD). Because polyamines may mediate some actions of hGH, we have nlow investigated polyamine metabolisimi in these and other dystrophies.Under metabolic balance study conditions, serum and urine levels of putrescine (Pu), spermidine (Sd), spermine (Smn), and cadaverine (Cd) were measured in six normal meni (36-44 yr), four men with MMD (38-44 yr), and three men with LGD (30-36 yr), before and durinig treatment with 0.532 U/kg body wt 314/d of hGH. Daily balances of N, P, and K were also monitored. In the normal subjects, hGH did not influence elemental balances or serum and urine polyamines. In MMD, hGH caused significant retention of N, P, and K (P < 0.005). Basal levels of Smn anid Cd were significantly elevated above niormal (P < 0.005), and Pu, Smn, and Cd increased two-to fourfold above basal during hGH treatment (P < 0.005). In LGD, hGH also caused retention of N, P, and K. Basal levels of nearly all the polyamiines (not serumi Pu) were significantly above normal in serum and urine (P < 0.05). During hGH treatmenit, all fotur polyamines rose significantly above basal (P < 0.005).Serum and urine polyaminie levels in five boys with Duchenne muscular dystrophy, age 8-13, did not differ from those in five age-matched normal boys.Skeletal muscle polyamines were measured in five men (31-40 yr) without muscle disease and in three meni with LGD (30-38 yr). Average concentrationis of Pu, Sd, Sm, and Cd were 46, 306, 548, and 61 nmol/g wet wt in LGD and 1, 121, 245, and 14 in the normnal subjects, respectively (P < 0.05 in each instance).Received for publication 9 Jutly 1979 and in revised form 14 September 1979. Polyamnines were determined in skeletal muscle, liver, kidnlley, and brain of male mice with hereditary muscular dystrophy and in age-and sex-mnatched normal controls. Pu, Sd, Sm, and Cd levels were two to three timiies higher than nonrnal in muscle, but did not differ in liver, kidney, and brain. Similar findings were made in miiale hamsters with hereditary dystrophy anid in their conitrols. The abnormality in hamster mnuscle polyamiinies appeared between 1 and 6 wk of age and( persisted or intensified until 30 wk.These data reveal abniormalities of polyamnine metabolism in men with MMD, in mnen with LGD, and in mice or hamsters with hereditary muscular dystrophy. The polyamine disorder could be related to dystrophic patients' hyperresponsiveness to hGH.

Methioninemia and myopathy: A new disorder

“…Since methionine also is a precursor of the polyamines [41], a defect in polyamine metabolism might lead to methionine accumulation. The recent observations of Kremzner et a1 [26] and of Rudman et a1 [39] suggest that this possibility is worth exploring, and such studies are now in progress.…”

Polyamines, androgens, and skeletal muscle hypertrophy

“…Polyamine levels are elevated in muscle from patients with Duchenne muscular dystrophy, in which the skeletal muscle is characterized by muscle fiber atrophy and hypertrophy, concurrent degeneration and regeneration, and connective tissue proliferation (Kaminska et al, 1981a). Limb girdle dystrophies patients, who have enlarged and split muscles fibers with widespread regeneration and degeneration (Kaminska et al, 1981a), also have higher levels of polyamines in skeletal muscle (Rudman et al, 1980; Kaminska et al, 1981a). Likewise, in mouse and hamster model of muscle dystrophy, levels of all three polyamines are higher than controls in muscle (Rudman et al, 1980).…”

Untargeted metabolomics for uncovering biological markers of human skeletal muscle ageing

“…Concomitantly overexpression of SMOX in C2C12 murine myotubes increases overall fibre size [58]. Moreover, in a number of neuromuscular disorders, an increased concentration of the polyamines and associated metabolites is often observed [59,60], highlighting their vital role in the skeletal muscle mass regulation, and indicating that they might be related to impaired regulation of muscle mass with ageing.…”