Regenerated mdx mouse skeletal muscle shows differential mRNA expression

Despite over 3,000 articles published on dystrophin in the last 15 years, the reasons underlying the progression of the human disease, differential muscle involvement, and disparate phenotypes in different species are not understood. The present experiment employed a screen of 12,488 mRNAs in 16-wk-old mouse mdx muscle at a time when the skeletal muscle is avoiding severe dystrophic pathophysiology, despite the absence of a functional dystrophin protein. A number of transcripts whose levels differed between the mdx and human Duchenne muscular dystrophy were noted. A fourfold decrease in myostatin mRNA in the mdx muscle was noted. Differential upregulation of actin-related protein 2/3 (subunit 4), β-thymosin, calponin, mast cell chymase, and guanidinoacetate methyltransferase mRNA in the more benign mdx was also observed. Transcripts for oxidative and glycolytic enzymes in mdx muscle were not downregulated. These discrepancies could provide candidates for salvage pathways that maintain skeletal muscle integrity in the absence of a functional dystrophin protein in mdx skeletal muscle.

Is hypoxia a stimulus for synthesis of oxidative enzymes and myoglobin?

To compare two situations with similar magnitudes of mitochondrial substrate flux but different blood oxygen contents, one-legged training was employed. Ten healthy subjects trained one leg under normobaric conditions and the other under hypobaric conditions. At each session the subjects trained each leg for 30 min. The absolute work intensity was the same for both legs and was chosen to correspond to 65% of the average (right and left) pretraining one-legged maximal work capacity. There were three to four training sessions per week for 4 wk. Muscle biopsies from each leg were taken before and after training and analyzed for fiber types, capillaries, myoglobin, and oxidative and glycolytic enzymes. The most striking finding was a greater increase of citrate synthase activity under hypobaric conditions than under normobaric conditions. In addition, the myoglobin content increased in the leg trained under hypobaric conditions, whereas it tended to decrease in the normobarically trained leg. Because both legs were trained at the same intensity, the oxygen turnover and the substrate flux through the carboxylic acid cycle and the respiratory chain must have been of similar magnitude. Thus a difference in substrate flux is less likely to have caused the differences in enzyme activities and myoglobin content between training under normobaric and hypobaric conditions. Instead, the stimulus seems to be related to the blood oxygen content or tension.

Metabolic fiber types of snake transversus abdominis muscle

Fibers of the garter snake transversus abdominis muscle fall into three classes according to contraction speed: faster and slower twitch and tonic. To determine the relationship between these physiologically determined classes and established mammalian fiber types, individual fibers were assayed for key enzymes representing the major energy-generating pathways in vertebrate muscle. Five such enzymes were examined: lactate dehydrogenase, malate dehydrogenase, adenylokinase, fumarate hydratase, and beta-hydroxyacyl-CoA dehydrogenase. The muscle contained three principal metabolic fiber types. Fast-contracting twitch fibers had low-oxidative but high-glycolytic capacity and therefore resembled mammalian-type fast-twitch glycolytic (FG) fibers. Slower twitch fibers were high oxidative-high glycolytic, similar to mammalian-type fast-twitch, oxidative, glycolytic (FOG) fibers. Tonic fibers were high oxidative-low glycolytic; this metabolic profile is characteristic of type slow-twitch oxidative (SO) fibers in mammals. Activity of the enzyme adenylokinase, which in mammals correlates with contraction speed and myosin adenosine triphosphatase (ATPase) activity, separated these reptilian fibers into three groups that are similar but not identical to those delineated by oxidative and glycolytic enzymes. Adenylokinase and beta-hydroxyacyl-CoA dehydrogenase showed the widest range of activities in snake muscle and, therefore, the greatest ability to discriminate fiber types.

Limits and constraints in the scaling of oxidative and glycolytic enzymes in homeotherms

It is now empirically well established that basal and maximum rates of O2 uptake in homeotherms scale approximately to the 0.75 power; log–log plots of mass-specific metabolic rates versus body mass yield slopes of −0.20 to 0.25. Recent studies of 10 mammalian species and 1 hummingbird species indicate that marker enzymes of mitochondrial metabolism (citrate synthase, for example) scale inversely with body mass. Hummingbirds and shrews are near the upper limit in the degree to which the oxidative capacity of heart and skeletal muscles can be elevated; further increases in mitochondrial volume densities would sacrifice myofilament or sarcoplasmic reticulum volume densities. Whales weighing about 105 kg may be near the limit at the opposite extreme because their mass-specific resting metabolic rates are predicted to be approaching those of hypometabolic ectotherms. In contrast to oxidative enzyme scaling patterns, enzymes normally operative in muscle anaerobic glycolysis, such as lactate dehydrogenase, scale directly with body mass. Hummingbirds and shrews are considered to have reduced muscle lactate dehydrogenase levels near a lower limit commensurate with buffering of cytosolic redox, a distinctly aerobic lactate dehydrogenase function. How much anaerobic glycolytic potential can be packed into muscle cells in the largest mammals is unknown; this upper limit appears to be set by a compromise between myofilament volume densities and the combined volume densities of glycogen granules, intracellular buffering components, and glycolytic enzymes.

Activities of oxidative and glycolytic enzymes in fetal heart, lung, and brain in the Weddell seal

The oxidative and glycolytic capacities of brain, heart, and lung in near-term Weddell seal fetuses were estimated from the maximal activities of four mitochondrial marker enzymes and four glycolytic enzymes. The catalyic potentials for both groups of enzymes were similar to adult levels in all three organs examined. It was concluded that the critical metabolic functions performed by these three central organs during diving are already fully developed in the fetal seal. This early development of adult-type metabolic machinery did not appear to be a preparatory step for later extrauterine function, but rather appeared to be necessary for times of normal maternal diving, when fetal metabolic responses mimic those of the mother.