摘要:

AbstractProtein kinase N (PKN) is a serine/threonine protein kinase rapidly activated by nerve growth factor (NGF) and other agents in various cell lines. The possible involvement of PKN in the multiple pathways of the NGF mechanism of action was previously established through the use of purine analogs, some of which are apparently specific inhibitors of this kinase. Since a PKN‐like activity is modulated in several cell lines by cAMP analogs and this activation requires the activity of cAMP‐dependent protein kinase. The aim of the present work is to investigate possible interactions between PKN and C‐PKA. Preincubation of the two kinases in the presence of ATP leads to potentiated phosphorylation of histone HF1, Kemptide (a substrate for C‐PKA, but not for PKN), and several additional substrates. This augmented phosphorylating activity is insensitive to 6‐thioguanine (an inhibitor for PKN, but not for C‐PKA) and is suppressed both by the Walsh inhibitor and by the regulatory subunit of PKA. PKN‐pretreated C‐PKA shows a significant decrease in Kmfor Kemptide and a substantial increase in Vmax. C‐PKA and PKN are widely expressed enzymes and the possibility of PKN‐dependent modulation of PKA in intact cells would therefore have biological implications for signal transduction mechanisms. ©

ISSN:0360-4012    

DOI:10.1002/jnr.490400112

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractSpinal cord explants from CD‐1 mouse embryos were cultured in Maximow slide assemblies to promote myelin development. At about 20 days in vitro, recombinant human or mouse tumor necrosis factor alpha (TNFa) was added. Observed 3–8 days later, myelin was largely intact. The myelin blistering and oligodendrocyte damage seen in other strains were generally absent. Axonal conduction was measured optically through the use of a voltage‐sensitive dye. Action potential shape, conduction velocity, and refractory period were all unchanged by exposure to TNFa. Two series of explants were grown with TNFa present continuously throughout the culture period. Observed with light and electron microscopy, myelin developed in at least 50% of the explants treated with recombinant mouse TNFα and 80% of those exposed to recombinant human TNFα. Optically recorded action potentials were of normal shape and refractory period. Conduction velocities were slightly lower than controls. CD‐1 mouse central nervous system contains TNFα receptors and yet was resistant to myelin damage. The apparent strain specificity of TNFα disruption of myelin may result from more indirect modes of action, including interaction with other cytokines produced by glial cells. Survival of axonal conduction suggest that Na+channel function remains intact following TNFα exposure. © 1995 Wi

ISSN:0360-4012    

DOI:10.1002/jnr.490400113

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractA number of cytokines and growth factors may affect astrocyte proliferation and functions. Transforming growth factor‐β1 (TGF‐β1) is a pleiotropic cytokine which exerts multiple effects on growth and differentiation of different cell types. TGF‐β1 is present in low amounts in the normal brain. TGF‐β1 gene expression, however, is increased in the central nervous system (CNS) in several pathological conditions. In this study we examined the in vitro effects of TGF‐β1 on the proliferative response of rat astrocytes to serum and growth factors. Astrocyte cultures were established from the cerebellum and cortex of newborn Lewis rats. The proliferative response of these cultures to serum and growth factors [platelet‐derived growth factor (PDGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin‐like growth factor 1 (IGF‐1), IGF‐2, interleukin 1 (IL‐1)] was studied by [3H]‐thymidine incorporation test in the presence or absence of TGF‐β1. TGF‐β1 significantly inhibited the proliferative response of astrocyte cultures to both autologous and heterologous serum. In addition, a strong inhibition of bFGF‐, EGF‐, and PDGF‐induced proliferation was observed. The effect of TGF‐β1 on the proliferative response to IL‐1 was less evident but still significant. No effect was observed when TGF‐β1 was added to IGF‐1 and IGF‐2 stimulated cultures. These data confirm previous reports showing a down‐regulating activity of TGF‐β on astrocyte proliferation and suggest that this cytokine may play physiological and pharmacological roles in the regulation of r

ISSN:0360-4012    

DOI:10.1002/jnr.490400114

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractGlutamic acid decarboxylase (GAD) catalyzes the biosynthesis of the inhibitory neurotransmitter γ‐aminobutyric acid (GABA). GAD has been suggested as an autoantigen in insulin‐dependent diabetes mellitus and stiff‐man syndrome. Recently, three forms of membrane‐associated GAD (MGAD) have been characterized in porcine brain, but the subcellular localization and function of these proteins are unknown. We present evidence that GAD activity is associated with synaptic vesicles from porcine brain. These vesicles contain a 60 kDa protein recognized by serum from patients with insulin‐dependent diabetes mellitus, probably MGADII, as shown by subcellular fractionation and immunoblotting. These results raise the possibility that the association of MGADII with synaptic vesicles may be crucial for its role as an autoantigen in insulin‐dependent diabetes mellitus. © 1995 Wi

ISSN:0360-4012    

DOI:10.1002/jnr.490400115

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractNeuropathy is an enigmatic and debilitating complication of diabetes. A consensus as to the pathogenesis of this disorder has yet to emerge. Recently, it has been found that the insulin‐like growth factors (IGFs) regulate peripheral nerve regeneration, and IGF content is reduced in various diabetic tissues. We tested herein the hypothesis that IGF administration can prevent or ameliorate the impairment of sensory nerve regeneration in streptozotocin diabetic rats. Miniosmotic pumps released small local doses of IGF‐I from a catheter routed near a site of sciatic nerve crush or larger systemic doses of IGF‐I or IGF‐II from a distant subcutaneous site. Whether administered locally or systemically, IGFs protected against the impairment of sensory nerve regeneration. Surprisingly, this protection was obtained despite unabated hyperglycemia. Therefore, the neuropathy involving sensory nerve regeneration in diabetes can be ameliorated or prevented by IGF treatment, independently of hyperglycemia. © 1995 Wiley

ISSN:0360-4012    

DOI:10.1002/jnr.490400116

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:0360-4012    

DOI:10.1002/jnr.490400101

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY