Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) and endostatin are angiogenic and anti-angiogenic molecules, respectively, that have been implicated in neurogenesis and neuronal survival. Using alkaline phosphatase fusion proteins, we show that the PC12 neuronal cell line contains cell membrane receptors for VEGF but not for endostatin and the collagen XV endostatin homologue. Immunocytochemistry confirmed that proliferating and differentiated PC12 cells express VEGF receptors 1, 2 and neuropilin-1. While no functional effects of VEGF on PC12 cell proliferation and differentiation could be observed, a slight VEGF-induced reduction of caspase-3 activity in differentiated apoptotic PC12 cells was paralleled by transient activation of ERK1/2 and Akt. In direct comparison, nerve growth factor proved to be a strikingly more potent neuroprotective agent than VEGF.
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PMID:VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor. 1673 52

Endostatin (ES), the C-terminal fragment of collagen XVIII known for its anti-angiogenic properties, is associated with neurological diseases in mammals. In this study, we investigated the effect of ES on nerve growth factor (NGF)-induced neuronal differentiation, migration, neuritogenesis, and neurite extension. ES partially inhibited PC12 cell differentiation and cerebellar granule cell migration. In addition, neurite outgrowth was inhibited in a concentration-dependent manner. This effect was also matrix-dependent, as we observed better inhibition on PC12 cells grown on collagen compared to laminin matrices. Furthermore, we observed partial NGF depletion by collagen and ES, but not by laminin suggesting that NGF-matrix interactions may be important for promoting neuritogenesis, competitive inhibition by ES or low affinity matrix impairs PC12 differentiation and neurite outgrowth. Finally, using a biosensor technique, we demonstrated a direct interaction between NGF and ES suggesting the mechanism of action of ES may involve NGF sequestration. In conclusion, our study demonstrates the inhibitory effect of ES on different steps of neurogenesis including cell differentiation and migration and neuritogenesis by NGF sequestration. Such sequestration may compromise brain repair following injury, but also may play important role in axon finding as well as a potent therapeutical target in diseases involving abnormal elevated neurotrophic growth factor levels. Taken together, this study raises the consideration of ES as a double-edge sword that carries both deleterious and putative therapeutical effects.
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PMID:Endostatin binds nerve growth factor and thereby inhibits neurite outgrowth and neuronal migration in-vitro. 2084 15