{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T15:13:34Z","timestamp":1778339614367,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,2,27]],"date-time":"2015-02-27T00:00:00Z","timestamp":1424995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Our and other studies have reported that homocysteine thiolactone (<jats:styled-content style=\"fixed-case\">HTL<\/jats:styled-content>) could induce endothelial dysfunction. However, the precise mechanism was largely unknown. In this study, we tested the most possible factor\u2010endoplasmic reticulum (<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>) stress, which was demonstrated to be involved in endothelial dysfunction in cardiovascular disease. Acetylcholine (Ach)\u2010induced endothelium\u2010dependent relaxation (<jats:styled-content style=\"fixed-case\">EDR<\/jats:styled-content>) and biochemical parameters were measured in rat isolated aorta. The level of reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> was designed by specific fluorescent probe <jats:styled-content style=\"fixed-case\">DCFH<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">DAF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FM DA<\/jats:styled-content> separately. The nuclear translocation of the <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB was studied by immune\u2010fluorescence. The <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression and protein expression of <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content>78\u2014a key indicator for the induction of <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress\u2014were assessed by real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and Western blot. Two <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress inhibitors\u20104\u2010<jats:styled-content style=\"fixed-case\">PBA<\/jats:styled-content> (5\u00a0m<jats:sc>m<\/jats:sc>) and Tudca (500\u00a0\u03bcg\/mL)\u2014significantly prevented <jats:styled-content style=\"fixed-case\">HTL<\/jats:styled-content>\u2014impaired <jats:styled-content style=\"fixed-case\">EDR<\/jats:styled-content> and increased <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> release, endothelial nitric oxide synthase (<jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">SOD<\/jats:styled-content> activity, decreased <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> production, <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content> activity, <jats:styled-content style=\"fixed-case\">NOX<\/jats:styled-content>\u20104 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MDA<\/jats:styled-content> level. We also found that 4\u2010<jats:styled-content style=\"fixed-case\">PBA<\/jats:styled-content> and Tudca blocked <jats:styled-content style=\"fixed-case\">HTL<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB activation thus inhibiting the downstream target gene production including <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 and <jats:styled-content style=\"fixed-case\">ICAM<\/jats:styled-content>\u20101. Simultaneously, <jats:styled-content style=\"fixed-case\">HTL<\/jats:styled-content> increased the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein level of <jats:styled-content style=\"fixed-case\">GRP<\/jats:styled-content>78. <jats:styled-content style=\"fixed-case\">HTL<\/jats:styled-content> could induce <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress leading to a downstream enhancement of oxidative stress and inflammation, which finally caused vascular endothelial dysfunction.<\/jats:p>","DOI":"10.1111\/fcp.12101","type":"journal-article","created":{"date-parts":[[2015,1,27]],"date-time":"2015-01-27T04:46:43Z","timestamp":1422334003000},"page":"252-259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The role of endoplasmic reticulum stress in endothelial dysfunction induced by homocysteine thiolactone"],"prefix":"10.1111","volume":"29","author":[{"given":"Shujin","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pharmacy Gan Su Provincial Hospital Lan Zhou 73000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Gan Su Provincial Hospital Lan Zhou 73000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shehua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Gan Su Provincial Hospital Lan Zhou 73000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Gan Su Provincial Hospital Lan Zhou 73000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Gan Su Provincial Hospital Lan Zhou 73000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Gan Su Provincial Hospital Lan Zhou 73000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,2,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/157488410790410551"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/1755-5922.12014"},{"key":"e_1_2_5_4_1","first-page":"155","article-title":"The pathophysiological hypothesis of homocysteine thiolactone\u2010mediated vascular disease","volume":"599","author":"Jakubowski H.","year":"2008","journal-title":"J. Physiol. Pharmacol."},{"key":"e_1_2_5_5_1","first-page":"392","article-title":"Protein homocysteinylation: a new mechanism of\u00a0atherogenesis?","volume":"59","author":"Be\u0142towski J.","year":"2005","journal-title":"Postepy Hig. Med. Dosw."},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-13209"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.08.006"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e31805c9410"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2013.01.006"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.224766"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2014.03.007"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.02.009"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.227819"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401451"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710791959783"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.17"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-387042-1.00005-8"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356318"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062887"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2009.07.004"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.5604\/17322693.1087521"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3721"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.01.014"},{"key":"e_1_2_5_24_1","first-page":"977","article-title":"Atheroprotective effects of antioxidants through inhibition of mitogen\u2010activated protein kinases","volume":"25","author":"Kyaw M.","year":"2004","journal-title":"Acta Pharmacol. Sin."},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.09.005"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001547"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01364.x"}],"container-title":["Fundamental &amp; Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffcp.12101","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.12101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T15:24:33Z","timestamp":1696173873000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/fcp.12101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,27]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1111\/fcp.12101"],"URL":"https:\/\/doi.org\/10.1111\/fcp.12101","archive":["Portico"],"relation":{},"ISSN":["0767-3981","1472-8206"],"issn-type":[{"value":"0767-3981","type":"print"},{"value":"1472-8206","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,27]]},"assertion":[{"value":"2014-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-01-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}