Neurotrophic activity of monomeric glucophosphoisomerase was blocked by human immunodeficiency virus (HIV-1) and peptides from HIV-1 envelope glycoprotein.
Glucophosphoisomerase (GPI), a glycolytic enzyme, was recently described to share 90% sequence homology with neuroleukin, a recently discovered growth factor which promotes motor neuron regeneration in vivo, survival of peripheral and central neurons in vitro, and affects B cell immunoglobulin synthesis. Interestingly, neuroleukin activity was described to be antagonized by the human immunodeficiency virus (HIV-1) envelope glycoprotein (gp120), with which neuroleukin was found to share partial sequence homology. In this study, reduced GPI demonstrated similar activity to neuroleukin in a novel bioassay using human and rat neuroblastoma cell lines. In the presence of reduced GPI, these cells were found to differentiate, in terms of enhanced neurite extension at a reduced proliferation rate. These results demonstrate the existence of a novel growth factor activity of an evolutionary ancient enzyme. The nonreduced commercial form of GPI, probably the dimer, was found to be inactive in this bioassay. Using the neuroblastoma cells model system, we further investigated the significance of the region of homology to HIV-1 envelope glycoprotein (gp120) as the putative binding site of GPI to its receptor on neuronal cells.
Mizrachi
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Y
Cedars-Sinai Medical Center, UCLA School of Medicine 90024.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005956:Glucose-6-Phosphate Isomerase / Q000494:pharmacology* / Q000502:physiology; D006133:Growth Substances / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D015488:HIV Antigens / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008222:Lymphokines / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009447:Neuroblastoma; D051381:Rats; D012191:Retroviridae Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects
D006133:Growth Substances; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D008222:Lymphokines; D009414:Nerve Growth Factors; D012191:Retroviridae Proteins; D005956:Glucose-6-Phosphate Isomerase