Global ETD Search

11	Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration Rainey-Smith, S.R., Andersson, D.A., Williams, R.J., Rattray, Marcus January 2010 (has links) No / The alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNFalpha) have both been implicated in motor neurone vulnerability in amyotrophic lateral sclerosis/motor neurone disease. TNFalpha has been reported to increase cell surface expression of AMPAR subunits to increase synaptic strength and enhance excitotoxicity, but whether this mechanism occurs in motor neurones is unknown. We used primary cultures of mouse motor neurones and cortical neurones to examine the interaction between TNFalpha receptor activation, GluR2 availability, AMPAR-mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFalpha (10 ng/mL, 15 min) caused a marked redistribution of both GluR1 and GluR2 to the cell surface as determined by cell surface biotinylation and immunofluorescence. Using fura-2-acetoxymethyl ester microfluorimetry, we showed that exposure to TNFalpha caused a rapid reduction in the peak amplitude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase-dependent manner, consistent with increased insertion of GluR2-containing AMPAR into the plasma membrane. This resulted in a protection of motor neurones against kainate-induced cell death. Our data therefore, suggest that TNFalpha acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in amyotrophic lateral sclerosis. Animals Biotinylation Blotting Western Calcium Metabolism Calcium signaling Drug effects Cell survival Drug effects Cells Cultured Excitatory amino acid agonists Toxicity Female Fluorescent antibody technique Kainic acid Antagonists & inhibitors Toxicity Mice Motor neurons Drug effects Nerve degeneration Pathology Neuroprotective agents Phosphatidylinositol 3-Kinases Pregnancy Receptors AMPA Antagonists & inhibitors Biosynthesis Genetics Receptors Cell surface Biosynthesis Receptors Tumor necrosis factor Drug effects Spectrometry Fluorescence Tumor necrosis factor-alpha Pharmacology p38 mitogen-activated protein kinases REF 2014
12	Bone morphogenetic proteins differentially regulate pigmentation in human skin cells Singh, Suman K., Abbas, Waqas A., Tobin, Desmond J. January 2012 (has links) No / Bone morphogenetic proteins (BMPs) are a large family of multi-functional secreted signalling molecules. Previously BMP2/4 were shown to inhibit skin pigmentation by downregulating tyrosinase expression and activity in epidermal melanocytes. However, a possible role for other BMP family members and their antagonists in melanogenesis has not yet been explored. In this study we show that BMP4 and BMP6, from two different BMP subclasses, and their antagonists noggin and sclerostin were variably expressed in melanocytes and keratinocytes in human skin. We further examined their involvement in melanogenesis and melanin transfer using fully matched primary cultures of adult human melanocytes and keratinocytes. BMP6 markedly stimulated melanogenesis by upregulating tyrosinase expression and activity, and also stimulated the formation of filopodia and Myosin-X expression in melanocytes, which was associated with increased melanosome transfer from melanocytes to keratinocytes. BMP4, by contrast, inhibited melanin synthesis and transfer to below baseline levels. These findings were confirmed using siRNA knockdown of BMP receptors BMPR1A/1B or of Myosin-X, as well as by incubating cells with the antagonists noggin and sclerostin. While BMP6 was found to use the p38MAPK pathway to regulate melanogenesis in human melanocytes independently of the Smad pathway, p38MAPK, PI3-K and Smad pathways were all involved in BMP6-mediated melanin transfer. This suggests that pigment formation may be regulated independently of pigment transfer. These data reveal a complex involvement of regulation of different members of the BMP family, their antagonists and inhibitory Smads, in melanocytes behaviour. Adult Aged Bone Morphogenetic Protein 4 Antagonists & inhibitors Metabolism Pharmacology Bone Morphogenetic Protein 6 Antagonists & inhibitors Metabolism Pharmacology Bone Morphogenetic Protein Receptors Coculture techniques Epidermis Drug effects Radiation effects Female Gene knockdown techniques Humans Keratinocytes Enzymology Melanins Biosynthesis Melanocytes Ultrastructure Middle aged Models Biological Monophenol Monooxygenase Myosins Pigmentation Pseudopodia Signal transduction Skin cytology Smad Proteins Ultraviolet rays Up-Regulation p38 Mitogen-Activated Protein Kinases REF 2014

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Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration

Bone morphogenetic proteins differentially regulate pigmentation in human skin cells