1,721,053 research outputs found
Characterization of smooth muscle-like cells derived from TSC2 human renal angiomyolipoma and their phenotype reversion
No full textGlycosaminoglycan supplementation promotes nerve regeneration and muscle reinnervation
No full textThis study shows that treatment of rats with exogenous glycosaminoglycans stimulates peripheral nerve regeneration, increases the abundance of mRNAs for myelin proteins and promotes muscle reinnervation, After the sciatic nerve had been crushed the number of regenerating axons in the distal stump was markedly and highly significantly increased by glycosaminoglycan treatment throughout the experimental period. The increased number of axons was correlated with increased axon and fibre (axon + myelin) diameter, The abundance of mRNAs for Po protein and myelin basic protein of regenerating nerves was also affected by treatment with glycosaminoglycans. The increase in mRNA was also observed in the contralateral unlesioned nerve, Such a phenomenon did not occur in saline-treated rats. Glycosaminoglycan treatment markedly increased the number of muscle fibres reinnervated and accelerated the restoration of muscle twitch tension elicited by nerve stimulation. The effect was particularly evident during the early stages (16 and 21 days after nerve crush) of muscle reinnervation
High opioid doses inhibit whereas low doses enhance neuritogenesis in PC12 cells
No full textExposure to opiates affects brain development, cell growth as well as in vitro cell differentiation [33,34]. Perinatal treatment with morphine has been reported to impair neuronal plasticity after neonatal lesion with 5,7-dihydroxytryptamine (5,7-DHT) [8]. This study has investigated the use of mu, delta and kappa opioid receptor ligands to examine the selective receptor mediated inhibition of PC12 neurite formation. Morphine and D-Ala(2),D-Leu(5)-enkephalin (DADLE) had a comparable inhibitory potency with a maximal effect at 1 mM concentration, while both naltrexone and naltrindole antagonized their effect at only 10 nM. D-Ala(2)-MePhe(4),Gly-ol(5)-enkephalin (DAMGO) showed only a transient inhibitory effect. The administration of 10 nM guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) prevented morphine inhibition. It is suggested that opiate inhibition of neuritogenesis may be mediated by a receptor with delta-like characteristics coupled to G proteins. On the other hand, the activation of this receptor with morphine at a very low concentration (1 pM) actually enhanced nerve growth factor (NGF) neurite promoting activity
Progressive and selective changes in neurotrophic factor expression and substance P axonal transport induced by perinatal diabetes: Protective action of antioxidant treatment
No full textDiabetes-induced embryo malformations and growth retardation are correlated with a variety of biochemical changes including oxidative stress. In this study, we show that the morphological alterations are correlated with progressive and selective changes of mRNA expression in specific neurotrophic factors. At embryological stage E-17, diabetes affected both embryo growth and NGF mRNA expression, which was reduced by as much as 90 and 56% in target tissues of sensory system such as tongue and intestine, respectively. The reduction in retina and heart was around 50%, Conversely, the mRNA expression of low-affinity neurotrophin receptor p75 was increased. At birth, BDNF mRNA expression was affected with a significant generalized reduction,while in vibrissae we observed a reduction of BDNF and p75 mRNAs and an increase of NGF. At postnatal day 14, pups from diabetic mothers showed reduced muscle levels of IGF-I, while we observed a partial impairment of substance P axonal transport at postnatal day 28, Treatment of diabetic mothers with silybin, a flavonoid with antioxidant properties, prevented most of the changes in neurotrophic factor expression and substance P axonal transport with no effects on hyperglycemia and embryo growth retardation. These results indicate that oxidative stress may influence neurotrophic factor synthesis in target territories during development. In addition, these data suggest that nervous system abnormalities observed in diabetic embryopathy may also derive by insufficient neurotrophic factor biosynthesis involving sequentially NGF in the embryo and BDNF and IGF-I in the early postnatal days, Insulin treatment of diabetic mothers normalized hyperglycemia and body growth, with consequent regular embryonic and postnatal development. (C) 1999 Wiley-Liss, Inc
Inhibition of high glucose-induced protein mono-ADP-ribosylation restores neuritogenesis and sodium-pump activity in SY5Y neuroblastoma cells
No full textThe exposure of SY5Y neuroblastoma cells to high concentrations of glucose, fructose, or galactose is an experimental model commonly used for in vitro evaluation of typical neuronal alterations observed in diabetes mellitus, In the present study, we observed that 2 weeks of exposure to high carbohydrate concentrations caused both a significant impairment in neurite formation induced by supplementation of retinoic acid or by subtraction of fetal calf serum to the culture medium and a marked reduction in Naf-K+-ATPase activity. However, only the exposure to high millimoles of glucose caused an enhancement of mono-ADP-ribosylation, typical of diabetes mellitus, affecting at leat five proteins. The concomitant exposure to high glucose and to silybin, a mono-ADP-ribosylation inhibitor, normalized the extent of ADP-ribosylation of the five proteins and counteracted the inhibitory effects of high glucose on Na+-pump activity and on neuritogenesis, Conversely, the supplementation of silybin did not prevent fructose and galactose inhibitory effects on Na+-pump activity and neurite formation. These data confirm those of previous reports suggesting a link between excessive protein mono-ADP-ribosylation and the onset of diabetic complications such as diabetic neuropathy, (C) 1999 Wiley-Liss, Inc
Neuroprotection, neuroregeneration, and interaction with insulin-like growth factor-I: Novel non-anticoagulant action of glycosaminoglycans
No full textWe present recent developments in the area of glycosaminoglycans (GAGs) and their possible interaction with insulin-like growth factor-I (IGF-I), GAGs are constituents of proteoglycans, and the combination of a core protein and a specific GAG makes a unique proteoglycan with a precise developmental pattern and with the ability to bind growth factors, This process is apparently regulated by the moiety of the peripheral GAGs, The supplementation of GAGs promotes neuritogenesis in vitro and stimulates nerve regrowth and muscle reinnervation, an effect correlated with an increase in trophic factor mRNA expression, In the case of neonatal nerve lesion, there is in addition an enhanced motor neuron survival, accompanied by higher levels of IGF-I in plasma and denervated muscle, The neurotrophic and neuroregenerative effects of exogenous GAGs were also observed in motor neuron disease in the wobbler mouse. (C) 1998 Wiley-Liss, Inc
DIABETIC NEUROPATHY IN THE RAT .1. ALCAR AUGMENTS THE REDUCED LEVELS AND AXOPLASMIC-TRANSPORT OF SUBSTANCE-P
No full textThis study examined the sciatic nerve axonal transport of substance P-like immunoreactivity (SPLI) and its basal content in stomach, sciatic nerve and lumbar spinal cord of 8- and 12-week alloxan-diabetic rats, respectively. One group of diabetic rats received acetyl-l-carnitine (ALCAR) throughout the experimental period. Alloxan treatment caused hyperglycemia and reduced body growth. Axonal transport of SPLI was studied by measurement of 24-hour accumulation at a ligature on the sciatic nerve. There was a marked reduction (from 50% to 100% according to the nerve segment examined) of anterograde and retrograde accumulation of SPLI in the constricted nerve of 8-week diabetic rats. In the sciatic nerve of ALCAR-treated diabetic rats, the accumulation of SPLI was comparable to control values. In the sciatic nerve, lumbar spinal cord and stomach of 12-week diabetic rats, there is a significant reduction of SPLI content. ALCAR treatment prevented SPLI loss in these tissues. Sciatic nerves showed the typical sorbitol increase and myo-inositol loss that were significantly counteracted by ALCAR. This study suggests that ALCAR treatment prevents diabetes-induced sensory neuropathy by improving altered metabolic pathways such as polyol activity and myo-inositol synthesis, and by preventing the reduction of synthesis and axonal transport of substance P. (C) 1995 Wiley-Liss, Inc
Molecular characterization of a glycosylphosphatidylinositol-linked ADP-ribosyltransferase from lymphocytes
No full textMono ADP-ribosyltransferases catalyze the transfer of the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD) to proteins. It was reported by Wang et al (J Immunol 153:4048, 1994) that incubation of mouse cytotoxic T lymphocytes (CTL) with NAD resulted in the ADP-ribosylation of membrane proteins and inhibition of cell proliferation and cytotoxicity. Treatment of CTL with phosphatidylinositol-specific phospholipase C (PI-PLC) before incubation with NAD prevented the inhibitory effects of NAD on the cells, consistent with the removal of a glycosylphosphatidylinositol (GPI)-anchored ADP-ribosyltransferase on the lymphocyte surface. We have identified and cloned a GPI-linked ADP-ribosyltransferase from Yac-1 mouse T-cell lymphoma cells. The deduced amino acid sequence of the Yac-1 transferase was 70% and 41% identical to those of the rabbit skeletal muscle and chicken heterophil, respectively. It contained three noncontiguous sequences similar to those found in several of the bacterial toxin and vertebrate ADP-ribosyltransferases. Based on crystallography of the bacterial toxins, these regions are believed to form, in part, the catalytic site consistent with a common mechanism for the ADP-ribose transfer reaction. In rat mammary adenocarcinoma (NMU) cells transformed with the Yac-1 transferase cDNA, transferase activity was present on the cell surface and was released into the medium by treatment of cells with PI-PLC. Thus, we have cloned a novel gene that has properties identical to the transferase detected in CTL, and may be involved in the NAD-dependent regulation of proliferation and cytotoxicit
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