RESUMO
Two sisters with progressive myopathy demonstrated microscopic and biochemical evidence of lipid storage in skeletal muscle. Their muscle biopsy specimens resembled those seen in Duchenne's muscular dystrophy and some of the biochemical features were similar, including increased muscle concentration of long-chain acyl-coenzyme A (a fatty oxidation intermediate) and decreased oxidation of radioactively labeled fatty acids by muscle homogenates in vitro. Although the site of the defect was not localized, the data suggested impairment of intramitochondrial beta-oxidation of fatty acids. These two patients may be important in understanding the pathogenesis of muscular dystrophy.
Assuntos
Metabolismo dos Lipídeos , Distrofias Musculares/metabolismo , Criança , Pré-Escolar , Coenzima A/metabolismo , Feminino , Humanos , Distrofias Musculares/enzimologia , Distrofias Musculares/genética , Distrofias Musculares/patologia , Oxirredução , Palmitatos/metabolismo , Piruvatos/metabolismoRESUMO
Compared with normal or denervated human muscle, long chain acyl CoA was increased in muscle from patients with Duchenne dystrophy. Free and short chain acylcarnitine were reduced in Duchenne muscle, whereas long chain acylcarnitine was preserved. The accumulation of long chain fatty acid derivatives may imply disruption of fatty acid oxidation.
Assuntos
Acil Coenzima A/metabolismo , Distrofias Musculares/enzimologia , Carnitina/metabolismo , HumanosRESUMO
The silicone chamber model was used to evaluate peripheral nerve regeneration (PNR) in streptozocin (STZ)-induced diabetic rats. Diabetic and control animals underwent sciatic nerve transection and silicone chamber implantation establishing gaps of various lengths between the transected nerve ends. In animals with 5 and 10 mm gaps, diabetes was induced in experimental rats 1 week before surgery, and the animals were sacrificed 3 weeks after surgery. In animals with 8 mm gaps, diabetes induction occurred 3 days after surgery, and they were sacrificed after 7 weeks. Diabetic rats with 10 mm gaps demonstrated an impaired ability to form bridging cables, the initial step of regeneration through chambers. Morphometric studies of bridging cables between transected nerve ends demonstrated a significant reduction in the mean endoneurial area in diabetic animals with 5 and 8 mm gaps compared to controls. The number of regenerated myelinated axons in the chamber was significantly decreased in diabetic rats with 8 and 10 mm gaps. The mean myelinated fiber area in the regenerated cables of the diabetic group was significantly decreased with 5 mm gaps and significantly increased with 8 mm gaps compared to controls. Size-frequency histograms of regenerated myelinated fiber areas suggest a delay in the maturation of small caliber axons. Schwann cell migration across 5 mm gaps was examined with S-100 immunohistochemistry. The total distance of Schwann cell migration into cables from both proximal and distal ends was significantly reduced in diabetic animals. Characterization of PNR across gaps through silicone chambers in diabetic rats showed impairment in multiple aspects of the regenerative process, including cable formation, Schwann cell migration, and axonal regeneration.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Regeneração Nervosa , Neurologia/instrumentação , Neurologia/métodos , Nervo Isquiático/fisiopatologia , Silicones , Animais , Movimento Celular , Feminino , Próteses e Implantes , Ratos , Ratos Sprague-Dawley , Células de Schwann/fisiologia , Nervo Isquiático/patologiaRESUMO
In vitro oxidation of U-[14C]glucose-6-phosphate, 2-[14C]pyruvate, and 1-[14C]pyruvate was significantly reduced in red skeletal muscle from fasting rats. Over the same time interval of fasting, 1-[14C]palmitate oxidation remained unchanged. Pyruvate dehydrogenase activity, assayed before in vitro activation, was also reduced in red muscle. Long chain acylcarnitine and long chain acyl CoA increased over the same time period in red muscle. Changes in long chain fatty acid derivatives and pyruvate oxidation were much less dramatic in white muscle. We propose that the rise in levels of long chain fatty acid derivatives may be directly related to the inhibition of carbohydrate oxidation during fasting in red skeletal muscle.
Assuntos
Jejum , Ácidos Graxos/metabolismo , Músculos/enzimologia , Animais , Carnitina/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Citrato (si)-Sintase/metabolismo , Coenzima A/metabolismo , Glucose-6-Fosfato , Glucofosfatos/metabolismo , Masculino , Oxirredução , Ácido Palmítico , Ácidos Palmíticos/metabolismo , Palmitoil-CoA Hidrolase/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Piruvatos/metabolismo , Ácido Pirúvico , Ratos , Ratos EndogâmicosRESUMO
We examined whether the short-term beneficial effects of nerve growth factor (NGF) upon regeneration are sustained over a prolonged period of time across 8-mm gaps within silicone chambers. Rat sciatic nerve regeneration both with and without NGF was examined after 10 weeks. Myelinated counts from the regenerated sciatic and distal tributary nerves were correlated to the numbers of motor and sensory neurons retrogradely labeled with horseradish peroxidase (HRP) applied distal to the regenerated segment. Regenerated sciatic and sural nerves were examined ultrastructurally for morphological analysis. Both regenerated groups by 10 weeks achieved essentially complete counts of myelinated axons in the distal tributary nerves and the regenerated segment of the sciatic nerve compared to the uninjured controls. There were similar numbers of retrogradely labeled sensory and motor neurons in the dorsal root ganglia (DRG) and lumbar spinal cord of both groups and, surprisingly, of the uninjured normal control group. Ultrastructural analysis demonstrated no difference in the distribution of axonal diameters or myelin thickness between the regenerated groups. In evaluating regeneration in experimental silicone chamber models, it is important to determine such parameters as the percentage of neurons that grow across the gap and the incidence of axonal sprouting. One can then make accurate assessments of experimental perturbations and predict whether they improve the naturally occurring regeneration through chambers. These results must ultimately be compared with equivalent determinations in the uninjured nerve. At 10 weeks there was essentially complete regeneration of both the NGF and control regenerative groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Axônios/fisiologia , Fatores de Crescimento Neural/farmacologia , Regeneração Nervosa , Nervo Isquiático/fisiologia , Animais , Axônios/ultraestrutura , Feminino , Gânglios Espinais/citologia , Peroxidase do Rábano Silvestre , Microscopia Eletrônica , Neurônios Motores/citologia , Bainha de Mielina/ultraestrutura , Neurologia/instrumentação , Neurônios Aferentes/citologia , Ratos , Ratos Endogâmicos , Nervo Isquiático/ultraestrutura , Silicones , Medula Espinal/citologia , Fatores de TempoRESUMO
(1-14C)-palmitate oxidation in rat skeletal muscle homogenates increased only minimally from birth until 15 days of age and then increased more than five times between 15 days and adulthood. In contrast, liver oxidation of palmitate reached adult levels by 4 days of age. Although muscle carnitine concentration, carnitine palmityl transferase activity, and total muscle protein increased during the neonatal period, these changes did not completely parallel the rise in muscle palmitate oxidation. Palmityl-CoA synthetase and palmityl-CoA dehydrogenase activities also did not parallel the rise in overall palmitate oxidation.
Assuntos
Ácidos Graxos/metabolismo , Músculos/metabolismo , Proteínas Repressoras , Proteínas de Saccharomyces cerevisiae , Acil-CoA Desidrogenase , Fatores Etários , Animais , Animais Recém-Nascidos , Carnitina/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Coenzima A Ligases/metabolismo , Ácidos Graxos Dessaturases/metabolismo , Fígado/metabolismo , Oxirredução , Ácido Palmítico , Ácidos Palmíticos/metabolismo , Ratos , Ratos EndogâmicosRESUMO
The ability of extracellular proteins to influence the regenerative process was examined in Sprague-Dawley rats. Silicon chambers, filled with sterile saline solutions of cytochrome-c, fibronectin, laminin, a combination of fibronectin and laminin, or nerve growth factor were surgically implanted between the severed ends of sciatic nerves to form gaps of 18 mm. Four months later, the various groups were examined to determine the success of regeneration. The incidence of cable formation that bridged the gap was similar in all groups. The group of animals that had implants containing the combination of fibronectin/laminin had increased numbers of myelinated axons in the regenerated segment within the chamber and in the distal sciatic tributary nerves. Horseradish peroxidase labelling demonstrated that increased numbers of sensory and motor neurons in the fibronectin/laminin group had regenerated axons across the gap into the distal tributaries of the sciatic nerve. The effect of the various agents on non-neuronal cells was measured by immunohistochemical staining with S-100 antibodies to determine the effects on Schwann cell migration. Silicon chambers, filled with sterile saline solutions of fibronectin, laminin, fibronectin/laminin, nerve growth factor, or cytochrome-c, were surgically implanted to form 5 mm gaps between severed sciatic nerve ends. Ten days later, Schwann cell migration into the bridging cables was examined in each group. Analysis revealed a greater influx of Schwann cells migrating into the regenerating segments in the fibronectin, the laminin, and the combination fibronectin/laminin groups compared to the control group (cytochrome-c).
Assuntos
Fibronectinas/fisiologia , Laminina/fisiologia , Regeneração Nervosa/fisiologia , Nervos Periféricos/fisiologia , Células de Schwann/citologia , Animais , Movimento Celular/fisiologia , Feminino , Técnicas Imunoenzimáticas , Ratos , Ratos Sprague-Dawley , SilícioRESUMO
Skeletal muscle lipid storage was induced by feeding rats brominated vegetable oil (BVO). The defect was examined by measuring radioactive substrate oxidation, intermediates of fatty acid oxidation, and activities of oxidative enzymes. One- and U-[14C] palmitate and 1-[14C] pyruvate oxidation were reduced in muscle after four doses of BVO. Inhibition of U-[14C] palmitate oxidation occurred after two doses. Short chain acylcoenzyme A(CoA) derivatives accumulated in the muscle. Several enzymes of beta-oxidation were significantly reduced, with the greatest reduction in 3-ketoacyl-CoA thiolase. The inhibition probably affected multiple sites of CoA and CoA-derivative metabolism.