Teneurin carboxy (C)-terminal associated peptide-1 inhibits alkalosis-associated necrotic neuronal death by stimulating superoxide dismutase and catalase activity in immortalized mouse hypothalamic cells.
The teneurins and the teneurin C-terminal-associated peptides (TCAP) are implicated in the regulation of neuron growth and differentiation. However, current observations suggest that TCAP-1 may also have a neuroprotective action during times of pH-induced cellular stress in the brain such as during hypoxia-ischemia and brain alkalosis. To test this hypothesis, we cultured a TCAP-1-responsive mouse hypothalamic cell line, N38, using media buffered at pHs 6.8, 7.4, 8.0 and 8.4 subsequently treated with 100 nM TCAP-1. TCAP-1 significantly inhibited the decline in cell proliferation at pHs 8.0 and 8.4 as determined by direct cell viability assays and decreased the incidence of cells showing necrotic morphology. In addition, TCAP-1 decreased the number of cells undergoing necrosis by 4- to 5-fold as measured by uptake of ethidium homodimer III. Moreover, TCAP-1 significantly decreased the incidence of superoxide radicals and increased superoxide dismutase 1 (SOD1) expression. These results were accompanied by an increase in the SOD copper chaperone expression and increased catalase activity and expression. The results indicate that TCAP may play a neuroprotective role during periods of pH stress by upregulating oxygen radical scavenging systems. Thus, the TCAP-teneurin system may be part of a mechanism to protect neurons during trauma, such as hypoxia and ischemia.
Trubiani
Gina
G
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
Al Chawaf
Arij
A
Belsham
Denise D
DD
Barsyte-Lovejoy
Dalia
D
Lovejoy
David A
DA
D000471:Alkalosis / Q000150:complications / Q000201:enzymology / Q000503:physiopathology; D000818:Animals; D002374:Catalase / Q000378:metabolism*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects; D016166:Free Radical Scavengers / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D051379:Mice; D009336:Necrosis / Q000188:drug therapy* / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016166:Free Radical Scavengers; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C500186:TCAP-1 protein, mouse; D013481:Superoxides; D002374:Catalase; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1