Mature pig oligodendrocytes rapidly process human recombinant pro-nerve growth factor and do not undergo cell death
| Autor: | H. H. Althaus, Sabine Klöppner |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Programmed cell death
medicine.medical_specialty Swine Blotting Western Tetrazolium Salts Tropomyosin receptor kinase A Biochemistry Cellular and Molecular Neuroscience Internal medicine Nerve Growth Factor medicine Low-affinity nerve growth factor receptor Animals Humans Protein Precursors Cells Cultured biology Cell Death Immunohistochemistry Oligodendrocyte Endocytosis Recombinant Proteins Cell biology Nerve Regeneration Oligodendroglia Thiazoles Endocrinology medicine.anatomical_structure Nerve growth factor nervous system Trk receptor biology.protein Neuroglia Mitogen-Activated Protein Kinases Neurotrophin Signal Transduction |
| Zdroj: | Journal of neurochemistry. 98(2) |
| ISSN: | 0022-3042 |
| Popis: | The neurotrophin family with its first member, nerve growth factor (NGF), binds two classes of receptors, more specifically to Trk receptors and to a shared p75NTR receptor. It has been shown that proNGF rather than NGF is predominant in the mature central nervous system. A recent finding indicated that a furin-resistant proNGF preferentially binds to p75NTR, initiating a pro-apoptotic cascade even in the presence of TrkA. In this context, rodent oligodendrocytes were reported to undergo cell death when exposed to proNGF. We have investigated the effect of a non-mutated 32 kDa human recombinant proNGF (rhproNGF) on cultured pig oligodendrocytes which express TrkA, p75NTR and sortilin. Pig oligodendrocytes respond to rhproNGF (50 ng/mL) with an enhanced regeneration of their processes as already observed for NGF. Activity of mitogen-activated protein kinase (MAPK), which plays an important role in oligodendroglial process formation, was increased even when rhproNGF processing was inhibited by the furin inhibitor Decanoyl-RVKR-CMK. Similarly, a cleavage-resistant proNGF (R-1G) activated MAPK and promoted oligodendroglial process regeneration. High concentrations of rhproNGF (300 ng/mL) did not induce cell death. Sodium dodecyl sulfate – polyacrylamide gel electrophoresis and Western blotting revealed that oligodendrocytes process rhproNGF to NGF. NGF was detected in Western blots of oligodendroglial lysates already 10 min after rhproNGF exposure, followed by a release of NGF into the culture medium. Indirect evidence indicates that rhproNGF processing occurs via an endocytotic route. |
| Databáze: | OpenAIRE |
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