PMID- 31652920 OWN - NLM STAT- MEDLINE DCOM- 20200415 LR - 20240109 IS - 1660-3397 (Electronic) IS - 1660-3397 (Linking) VI - 17 IP - 11 DP - 2019 Oct 24 TI - Pyrogallol-Phloroglucinol-6,6-Bieckol from Ecklonia cava Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation Injury. LID - 10.3390/md17110602 [doi] LID - 602 AB - 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 Ecklonia cava (E. cava) would attenuate TEC death induced by H/R injury. We also evaluated which phlorotannin-dieckol (DK), phlorofucofuroeckol A (PFFA), pyrogallol phloroglucinol-6,6-bieckol (PPB), or 2,7-phloroglucinol-6,6-bieckol (PHB)-would have the most potent effect in the context of H/R injury. We used for pre-hypoxia treatment, in which the phlorotannins from E. cava 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-alpha 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-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. FAU - Son, Myeongjoo AU - Son M AUID- ORCID: 0000-0002-9104-3991 AD - Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea. mjson@gachon.ac.kr. AD - Functional Cellular Networks Laboratory, College of Medicine, Department of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea. mjson@gachon.ac.kr. FAU - Oh, Seyeon AU - Oh S AD - Functional Cellular Networks Laboratory, College of Medicine, Department of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea. seyeon8965@gachon.ac.kr. FAU - Choi, Chang Hu AU - Choi CH AD - Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea. cch624@gilhospital.com. FAU - Park, Kook Yang AU - Park KY AD - Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea. kkyypark@gilhospital.com. FAU - Son, Kuk Hui AU - Son KH AD - Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea. dr632@gilhospital.com. FAU - Byun, Kyunghee AU - Byun K AD - Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea. khbyun1@gachon.ac.kr. AD - Functional Cellular Networks Laboratory, College of Medicine, Department of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea. khbyun1@gachon.ac.kr. LA - eng GR - 20170285/Ministry of Oceans and Fisheries/ PT - Journal Article DEP - 20191024 PL - Switzerland TA - Mar Drugs JT - Marine drugs JID - 101213729 RN - 0 (Cytokines) RN - 0 (Dioxins) RN - 0 (HMGB1 Protein) RN - 0 (NF-kappa B) RN - 0 (Tannins) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 01Y4A2QXY0 (Pyrogallol) RN - 88095-81-2 (6,6'-bieckol) SB - IM MH - Animals MH - Cell Line MH - Cytokines/metabolism MH - Dioxins/pharmacology MH - Epithelial Cells/drug effects MH - HMGB1 Protein/metabolism MH - Hypoxia/chemically induced/*drug therapy MH - Kidney/metabolism MH - MAP Kinase Signaling System/drug effects MH - Mice MH - NF-kappa B/metabolism MH - Phaeophyceae/*chemistry MH - Pyrogallol/*pharmacology MH - Signal Transduction MH - Tannins/pharmacology MH - Toll-Like Receptor 4/metabolism PMC - PMC6891818 OTO - NOTNLM OT - Ecklonia cava OT - ischemia-reperfusion injury OT - kidney OT - phlorotannins COIS- The authors have no conflict of interest to declare. EDAT- 2019/10/28 06:00 MHDA- 2020/04/16 06:00 PMCR- 2019/11/01 CRDT- 2019/10/27 06:00 PHST- 2019/09/25 00:00 [received] PHST- 2019/10/21 00:00 [revised] PHST- 2019/10/22 00:00 [accepted] PHST- 2019/10/27 06:00 [entrez] PHST- 2019/10/28 06:00 [pubmed] PHST- 2020/04/16 06:00 [medline] PHST- 2019/11/01 00:00 [pmc-release] AID - md17110602 [pii] AID - marinedrugs-17-00602 [pii] AID - 10.3390/md17110602 [doi] PST - epublish SO - Mar Drugs. 2019 Oct 24;17(11):602. doi: 10.3390/md17110602.