Signaling mechanisms of HIV-1 Tat-induced alterations of claudin-5 expression in brain endothelial cells
Exposure of brain microvascular endothelial cells (BMEC) to human immunodeficiency virus-1 (HIV-1) Tat protein can decrease expression and change distribution of tight junction proteins, including claudin-5. Owing to the importance of claudin-5 in maintaining the blood-brain barrier (BBB) integrity, the present study focused on the regulatory mechanisms of Tat-induced alterations of claudin-5 mRNA and protein levels. Real-time reverse-transcription-polymerase chain reaction revealed that claudin-5 mRNA was markedly diminished in BMEC exposed to Tat. However, U0126 (an inhibitor of mitogen-activated protein kinase kinase1/2, MEK1/2) protected against this effect. In addition, inhibition of the vascular endothelial growth factor receptor type 2 (VEGFR-2) by SU1498, phosphatidylinositol-3 kinase (PI-3 K) by LY294002, nuclear factor-kappaB (NF-kappaB) by peptide SN50, and intracellular calcium by BAPTA/AM partially prevented Tat-mediated alterations in claudin-5 protein levels and immunoreactivity patterns. In contrast, inhibition of protein kinase C did not affect claudin-5 expression in Tat-treated cells. The present findings indicate that activation of VEGFR-2 and multiple redox-regulated signal transduction pathways are involved in Tat-induced alterations of claudin-5 expression. Because claudins constitute the major backbone of tight junctions, the present data are relevant to the disturbances of the BBB in the course of HIV-1 infection.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2005 |
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| Erschienen: |
2005 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism - 25(2005), 9 vom: 08. Sept., Seite 1159-70 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
András, Ibolya E [VerfasserIn] |
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| Anmerkungen: |
Date Completed 21.09.2005 Date Revised 09.03.2022 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM154662208 |
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| 100 | 1 | |a András, Ibolya E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Signaling mechanisms of HIV-1 Tat-induced alterations of claudin-5 expression in brain endothelial cells |
| 264 | 1 | |c 2005 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
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| 500 | |a Date Completed 21.09.2005 | ||
| 500 | |a Date Revised 09.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Exposure of brain microvascular endothelial cells (BMEC) to human immunodeficiency virus-1 (HIV-1) Tat protein can decrease expression and change distribution of tight junction proteins, including claudin-5. Owing to the importance of claudin-5 in maintaining the blood-brain barrier (BBB) integrity, the present study focused on the regulatory mechanisms of Tat-induced alterations of claudin-5 mRNA and protein levels. Real-time reverse-transcription-polymerase chain reaction revealed that claudin-5 mRNA was markedly diminished in BMEC exposed to Tat. However, U0126 (an inhibitor of mitogen-activated protein kinase kinase1/2, MEK1/2) protected against this effect. In addition, inhibition of the vascular endothelial growth factor receptor type 2 (VEGFR-2) by SU1498, phosphatidylinositol-3 kinase (PI-3 K) by LY294002, nuclear factor-kappaB (NF-kappaB) by peptide SN50, and intracellular calcium by BAPTA/AM partially prevented Tat-mediated alterations in claudin-5 protein levels and immunoreactivity patterns. In contrast, inhibition of protein kinase C did not affect claudin-5 expression in Tat-treated cells. The present findings indicate that activation of VEGFR-2 and multiple redox-regulated signal transduction pathways are involved in Tat-induced alterations of claudin-5 expression. Because claudins constitute the major backbone of tight junctions, the present data are relevant to the disturbances of the BBB in the course of HIV-1 infection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Chelating Agents |2 NLM | |
| 650 | 7 | |a Claudin-5 |2 NLM | |
| 650 | 7 | |a Cldn5 protein, rat |2 NLM | |
| 650 | 7 | |a Gene Products, tat |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a tat Gene Products, Human Immunodeficiency Virus |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor Receptor-2 |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Calcium |2 NLM | |
| 650 | 7 | |a SY7Q814VUP |2 NLM | |
| 700 | 1 | |a Pu, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Deli, Mária A |e verfasserin |4 aut | |
| 700 | 1 | |a Nath, Avindra |e verfasserin |4 aut | |
| 700 | 1 | |a Hennig, Bernhard |e verfasserin |4 aut | |
| 700 | 1 | |a Toborek, Michal |e verfasserin |4 aut | |
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