{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T16:07:44Z","timestamp":1785600464325,"version":"3.56.0"},"reference-count":55,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102017R1D1A1B03031468"],"award-info":[{"award-number":["NRF\u20102017R1D1A1B03031468"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102020R1I1A3074045"],"award-info":[{"award-number":["NRF\u20102020R1I1A3074045"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102018R1A2B6004598"],"award-info":[{"award-number":["NRF\u20102018R1A2B6004598"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI18C0920"],"award-info":[{"award-number":["HI18C0920"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (H<jats:sub>2<\/jats:sub>S) produced by cystathionine \u03b3\u2010lyase (CSE) promotes vascular relaxation and lowers hypertension. Honokiol (HNK), a natural compound in the <jats:italic>Magnolia<\/jats:italic> plant, has been shown to retain multifunctional properties such as anti\u2010oxidative and anti\u2010inflammatory activities. However, a potential role of HNK in regulating CSE and hypertension remains largely unknown. Here, we aimed to demonstrate that HNK co\u2010treatment attenuated the vasoconstriction, hypertension and H<jats:sub>2<\/jats:sub>S reduction caused by angiotensin II (AngII), a well\u2010established inducer of hypertension. We previously found that histone deacetylase 6 (HDAC6) mediates AngII\u2010induced deacetylation of CSE, which facilitates its ubiquitination and proteasomal degradation. Our current results indicated that HNK increased endothelial CSE protein levels by enhancing its stability in a sirtuin\u20103\u2010independent manner. Notably, HNK could increase CSE acetylation levels by inhibiting HDAC6 catalytic activity, thereby blocking the AngII\u2010induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination occurred mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was resistant to both acetylation and ubiquitination, exhibiting higher protein stability than that of wild\u2010type CSE. Collectively, our findings suggested that HNK treatment protects CSE against HDAC6\u2010mediated degradation and may constitute an alternative for preventing endothelial dysfunction and hypertensive disorders.<\/jats:p>","DOI":"10.1111\/jcmm.15686","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T01:15:51Z","timestamp":1596590151000},"page":"10663-10676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Honokiol ameliorates angiotensin II\u2010induced hypertension and endothelial dysfunction by inhibiting HDAC6\u2010mediated cystathionine \u03b3\u2010lyase degradation"],"prefix":"10.1111","volume":"24","author":[{"given":"Zhexi","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine Ajou University School of Medicine Suwon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Truc Phan Hoang","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Ajou University Graduate School of Medicine Suwon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Ki","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Sport Science Chungnam National University Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erling","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Sport Science Chungnam National University Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine Hallym University Dongtan Sacred Heart Hospital Hwaseong Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanha","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy Gachon University Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Yong","family":"Seo","sequence":"additional","affiliation":[{"name":"College of Pharmacy Gachon University Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sook Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine Ajou University School of Medicine Suwon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine Hallym University Dongtan Sacred Heart Hospital Hwaseong Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4695-0266","authenticated-orcid":false,"given":"Sang Yoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Ajou University Graduate School of Medicine Suwon Korea"},{"name":"Institute for Medical Sciences Ajou University School of Medicine Suwon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa0903829"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2541"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4433"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.300505"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2014.01.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3391"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1162667"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14446"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.02.033"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002208"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2015.05.007"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08964"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.04.005"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04874-4"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14684"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00149.2014"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00724.2016"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14188"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv265"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104281"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/417455a"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.04.021"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.05.033"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.07.036"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.2.753"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7656"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1750306"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2012.01.001"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13689"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.c19-00207"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605545103"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00282.2016"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202916109"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/21224"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt065"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.05.006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2007.06.009"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2005.09.010"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.214"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.476"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4585"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9494052"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803749105"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.05.021"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-018-0937-x"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.01.040"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf682"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep19626"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2015.03.018"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00357"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja102758v"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27200"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.12.023"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018713"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1656-6"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.15686","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.15686","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.15686","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T16:59:24Z","timestamp":1692550764000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.15686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,4]]},"references-count":55,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1111\/jcmm.15686"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.15686","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,4]]},"assertion":[{"value":"2020-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}