Brain heparanase expression is up-regulated during postnatal development and hypoxia-induced neovascularization in adult rats
| Autor: | Jérémie Nadam, Fabrice P Navarro, Béatrice Georges, Pascal E. Sanchez, Jean-Marc Pequignot, Laurent Bezin, Colette Moulin, Anne Morales, Raafat P. Fares |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Angiogenesis Cell Antigens CD34 Biology Environment Biochemistry PC12 Cells Neovascularization Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Downregulation and upregulation Internal medicine Gene expression Nerve Growth Factor medicine Animals Heparanase RNA Messenger Hypoxia Ischemic Preconditioning Glucuronidase Regulation of gene expression Analysis of Variance Neovascularization Pathologic Age Factors Brain Gene Expression Regulation Developmental Cell Differentiation Cell biology Rats Vascular endothelial growth factor Disease Models Animal medicine.anatomical_structure Endocrinology chemistry Animals Newborn Bromodeoxyuridine medicine.symptom |
| Zdroj: | Journal of neurochemistry. 105(1) |
| ISSN: | 1471-4159 |
| Popis: | Heparanase is an endo-beta-d-glucuronidase which specifically cleaves extracellular and cell surface heparan sulphates at intra-chain sites. Its enzymatic activity is strongly implicated in cell dissemination associated with tumor metastasis and inflammation. Indeed, heparanase gene is expressed in various tumors and its over-expression is correlated with increased tumor vascularity and metastatic potential of tumor cells. However, heparanase expression in non-invasive and non-immune tissue, including brain, has received less attention. Using RT-qPCR, western blot and histological analysis, we demonstrate in the adult rat that heparanase transcript is differentially expressed according to brain area, and that heparanase protein is mainly detected in neurons. Furthermore, we provide evidence that heparanase transcript and protein reach their greatest levels at early postnatal stages, in particular within the neocortex characterized by intensive structural plasticity. Using the in vitro model of PC12-induced neuronal differentiation, we suggest that developmental regulation of heparanase may coincide with axonal and dendritic pathfinding. At adulthood, we demonstrate that the increased heparanase transcript level correlates in the hippocampus with enhanced angiogenesis following repeated hypoxia exposures. Taken together, our results emphasize the potential importance of heparanase in brain homeostasis, both during development and adaptative responses to severe environmental challenges. |
| Databáze: | OpenAIRE |
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