Osmotic swelling induces p75 neurotrophin receptor (p75NTR) expression via nitric oxide.
Brain injuries by physical trauma, epileptic seizures, or microbial infection upset the osmotic homeostasis resulting in cell swelling (cerebral edema), inflammation, and apoptosis. Expression of the neurotrophin receptor p75NTR is increased in the injured tissue and axon regeneration is repressed by the Nogo receptor using p75NTR as the signal transducer. Hence, p75NTR seems central to the injury response and we wished to determine the signals that regulate its expression. Here, we demonstrate that tonicity mediated cell swelling rapidly activates transcription of the endogenous p75NTR gene and of a p75NTR promoter-reporter gene in various cell types. Transcription activation is independent of de novo protein synthesis and requires the activities of phospholipase C, protein kinase C, and nitric-oxide synthase. Hence, p75NTR is a nitric oxide effector gene regulated by osmotic swelling, thereby providing a strategy for therapeutic intervention to modulate p75NTR functions following injury.
Peterson
Suzanne
S
Childrens Hospital of Los Angeles, Division of Hematology and Oncology, Los Angeles, California 90027, USA.
Bogenmann
Emil
E
D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D009185:Myelin Proteins / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D000070798:Nogo Proteins; D009995:Osmosis; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D003432:Cross-Linking Reagents; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D009569:Nitric Oxide; D004533:Egtazic Acid; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester