Pyrogallol-Phloroglucinol-6,6-Bieckol from <i>Ecklonia cava</i> Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation Injury

The hypoxia/reoxygenation (H/R) injury causes serious complications after the blood supply to the kidney is stopped during surgery. The main mechanism of I/R injury is the release of high-mobility group protein B1 (HMGB1) from injured tubular epithelial cells (TEC, TCMK-1 cell), which triggers TLR4...

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Main Authors: Myeongjoo Son, Seyeon Oh, Chang Hu Choi, Kook Yang Park, Kuk Hui Son, Kyunghee Byun
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/17/11/602
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author Myeongjoo Son
Seyeon Oh
Chang Hu Choi
Kook Yang Park
Kuk Hui Son
Kyunghee Byun
author_facet Myeongjoo Son
Seyeon Oh
Chang Hu Choi
Kook Yang Park
Kuk Hui Son
Kyunghee Byun
author_sort Myeongjoo Son
collection DOAJ
description The hypoxia/reoxygenation (H/R) injury causes serious complications after the blood supply to the kidney is stopped during surgery. The main mechanism of I/R injury is the release of high-mobility group protein B1 (HMGB1) from injured tubular epithelial cells (TEC, TCMK-1 cell), which triggers TLR4 or RAGE signaling, leading to cell death. We evaluated whether the extracts of <i>Ecklonia cava (E. cava)</i> would attenuate TEC death induced by H/R injury. We also evaluated which phlorotannin&#8212;dieckol (DK), phlorofucofuroeckol A (PFFA), pyrogallol phloroglucinol-6,6-bieckol (PPB), or 2,7-phloroglucinol-6,6-bieckol (PHB)&#8212;would have the most potent effect in the context of H/R injury. We used for pre-hypoxia treatment, in which the phlorotannins from <i>E. cava</i> extracts were added before the onset of hypoxia, and a post- hypoxia treatment, in which the phlorotannins were added before the start of reperfusion. PPB most effectively reduced HMGB1 release and the expression of TLR4 and RAGE induced by H/R injury in both pre- and post-hypoxia treatment. PPB also most effectively inhibited the expression of NF-kB and release of the inflammatory cytokines TNF-&#945; and IL-6 in both models. PPB most effectively inhibited cell death and expression of cell death signaling molecules such as Erk/pErk, JNK/pJNK, and p38/pp38. These results suggest that PPB blocks the HGMB1&#8722;TLR4/RAGE signaling pathway and decreases TEC death induced by H/R and that PPB can be a novel target for renal H/R injury therapy.
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spelling doaj.art-691c11a4b3d8464b8cf1038f1ec448972022-12-22T04:22:23ZengMDPI AGMarine Drugs1660-33972019-10-01171160210.3390/md17110602md17110602Pyrogallol-Phloroglucinol-6,6-Bieckol from <i>Ecklonia cava</i> Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation InjuryMyeongjoo Son0Seyeon Oh1Chang Hu Choi2Kook Yang Park3Kuk Hui Son4Kyunghee Byun5Department of Anatomy &amp; Cell Biology, Gachon University College of Medicine, Incheon 21936, KoreaFunctional Cellular Networks Laboratory, College of Medicine, Department of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, KoreaDepartment of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, KoreaDepartment of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, KoreaDepartment of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, KoreaDepartment of Anatomy &amp; Cell Biology, Gachon University College of Medicine, Incheon 21936, KoreaThe hypoxia/reoxygenation (H/R) injury causes serious complications after the blood supply to the kidney is stopped during surgery. The main mechanism of I/R injury is the release of high-mobility group protein B1 (HMGB1) from injured tubular epithelial cells (TEC, TCMK-1 cell), which triggers TLR4 or RAGE signaling, leading to cell death. We evaluated whether the extracts of <i>Ecklonia cava (E. cava)</i> would attenuate TEC death induced by H/R injury. We also evaluated which phlorotannin&#8212;dieckol (DK), phlorofucofuroeckol A (PFFA), pyrogallol phloroglucinol-6,6-bieckol (PPB), or 2,7-phloroglucinol-6,6-bieckol (PHB)&#8212;would have the most potent effect in the context of H/R injury. We used for pre-hypoxia treatment, in which the phlorotannins from <i>E. cava</i> extracts were added before the onset of hypoxia, and a post- hypoxia treatment, in which the phlorotannins were added before the start of reperfusion. PPB most effectively reduced HMGB1 release and the expression of TLR4 and RAGE induced by H/R injury in both pre- and post-hypoxia treatment. PPB also most effectively inhibited the expression of NF-kB and release of the inflammatory cytokines TNF-&#945; and IL-6 in both models. PPB most effectively inhibited cell death and expression of cell death signaling molecules such as Erk/pErk, JNK/pJNK, and p38/pp38. These results suggest that PPB blocks the HGMB1&#8722;TLR4/RAGE signaling pathway and decreases TEC death induced by H/R and that PPB can be a novel target for renal H/R injury therapy.https://www.mdpi.com/1660-3397/17/11/602kidneyischemia-reperfusion injury<i>ecklonia cava</i>phlorotannins
spellingShingle Myeongjoo Son
Seyeon Oh
Chang Hu Choi
Kook Yang Park
Kuk Hui Son
Kyunghee Byun
Pyrogallol-Phloroglucinol-6,6-Bieckol from <i>Ecklonia cava</i> Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation Injury
Marine Drugs
kidney
ischemia-reperfusion injury
<i>ecklonia cava</i>
phlorotannins
title Pyrogallol-Phloroglucinol-6,6-Bieckol from <i>Ecklonia cava</i> Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation Injury
title_full Pyrogallol-Phloroglucinol-6,6-Bieckol from <i>Ecklonia cava</i> Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation Injury
title_fullStr Pyrogallol-Phloroglucinol-6,6-Bieckol from <i>Ecklonia cava</i> Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation Injury
title_full_unstemmed Pyrogallol-Phloroglucinol-6,6-Bieckol from <i>Ecklonia cava</i> Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation Injury
title_short Pyrogallol-Phloroglucinol-6,6-Bieckol from <i>Ecklonia cava</i> Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation Injury
title_sort pyrogallol phloroglucinol 6 6 bieckol from i ecklonia cava i attenuates tubular epithelial cell tcmk 1 death in hypoxia reoxygenation injury
topic kidney
ischemia-reperfusion injury
<i>ecklonia cava</i>
phlorotannins
url https://www.mdpi.com/1660-3397/17/11/602
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