Minocycline ameliorates hypoxia-induced blood–brain barrier damage by inhibition of HIF-1α through SIRT-3/PHD-2 degradation pathway

Highlights • Our results show that minocycline reduces hypoxia-induced increases in BBB permeability and HIF-1α. • Minocycline also increases the hypoxia-induced reduction of PHD-2 and SIRT-3. • These effects of minocycline are abolished by siRNA-mediated knockdown of SIRT-3 in the brain. • Minocycl...

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Veröffentlicht in:	Neuroscience 2015-09, Vol.304, p.250-259
Hauptverfasser:	Yang, F, Zhou, L, Wang, D, Wang, Z, Huang, Q.-Y
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Blood-Brain Barrier - drug effects Blood-Brain Barrier - metabolism Blood-Brain Barrier - pathology blood–brain barrier Cell Hypoxia - drug effects Cell Hypoxia - physiology Cells, Cultured Disease Models, Animal Endothelial Cells - drug effects Endothelial Cells - metabolism Endothelial Cells - pathology Gene Knockdown Techniques HIF-1α hypoxia Hypoxia, Brain - drug therapy Hypoxia, Brain - metabolism Hypoxia, Brain - pathology Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Hypoxia-Inducible Factor-Proline Dioxygenases - metabolism Male minocycline Minocycline - pharmacology neuro-inflammation Neurology Neuroprotective Agents - pharmacology Procollagen-Proline Dioxygenase - metabolism Rats, Sprague-Dawley RNA, Messenger - metabolism RNA, Small Interfering Signal Transduction - drug effects Signal Transduction - physiology SIRT-3 Sirtuin 3 - genetics Sirtuin 3 - metabolism Sirtuins - genetics Sirtuins - metabolism
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Zusammenfassung:	Highlights • Our results show that minocycline reduces hypoxia-induced increases in BBB permeability and HIF-1α. • Minocycline also increases the hypoxia-induced reduction of PHD-2 and SIRT-3. • These effects of minocycline are abolished by siRNA-mediated knockdown of SIRT-3 in the brain. • Minocycline inhibits HIF-1α-mediated cellular responses and protects the BBB through a SIRT-3/PHD-2-dependent pathway.
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2015.07.051