{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T16:58:48Z","timestamp":1781197128183,"version":"3.54.1"},"reference-count":39,"publisher":"Portland Press Ltd.","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["22K07466, 25K10657"],"award-info":[{"award-number":["22K07466, 25K10657"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"crossref","award":["JPMJSP2120"],"award-info":[{"award-number":["JPMJSP2120"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,21]]},"abstract":"<jats:p>Hyperhomocysteinemia is a risk factor of cardiovascular disease (CVD). High-density lipoprotein (HDL) plays an important role in anti-atherosclerosis, with its anti-atherogenic function attributed to HDL-associated proteins such as apolipoprotein A-I (apoA-I) and paraoxonase 1 (PON1). Homocysteine (Hcy) thiolactone modifies lysine residues in proteins, thereby altering their function. Although dysfunction of apoA-I and PON1 has been reported, the precise modification sites and underlying mechanisms have remained unclear. In this study, we aimed to identify Hcy-thiolactone modification sites on apoA-I and PON1. In addition, we sought to clarify the effects of Hcy-thiolactone on PON1 activity and its distribution. Modification sites were analyzed using MALDI-TOF MS. The effects of Hcy-thiolactone on various specimens, including purified proteins, reconstituted HDL (rHDL), HDL collected by ultracentrifugation, and serum samples, were characterized using enzymatic assays measuring three major PON1 activities (arylesterase, paraoxonase, and lactonase) and Western blotting. Our results demonstrated that while some Hcy-thiolactone modification sites were detected on apoA-I, PON1 itself was not directly modified by Hcy-thiolactone. Thiolactonase activity was reduced by Hcy-thiolactone in large HDL particles. Furthermore, a general reduction of PON1 activity and changes in HDL remodeling and distribution were observed in serum samples treated with Hcy-thiolactone. These findings suggest that PON1 dysfunction induced by Hcy-thiolactone is influenced by alterations in HDL remodeling and the enzyme\u2019s distribution on HDL particles. Analysis of PON1\u2019s distribution dynamics under pathological conditions may provide crucial insights into the mechanism of HDL function decline in CVD.<\/jats:p>","DOI":"10.1042\/bsr20253768","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:38:46Z","timestamp":1767771526000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Homocysteine thiolactone affects paraoxonase 1 activity via altered paraoxonase 1 distribution on high-density lipoprotein particles"],"prefix":"10.1042","volume":"46","author":[{"given":"Rina","family":"Kawaguchi","sequence":"first","affiliation":[{"name":"1Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunehiro","family":"Miyakoshi","sequence":"additional","affiliation":[{"name":"1Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"PhD","given":"Akira","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"1Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"PhD","given":"Shoichi","family":"Hosoya","sequence":"additional","affiliation":[{"name":"2Ochanomizu Research Facility, Bioscience Center, Research Infrastructure Management Center, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kugii","sequence":"additional","affiliation":[{"name":"3Department of Biochemical Pathophysiology, Medical Research Laboratory, Institute for Integrated Research, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"PhD","given":"Takehiko","family":"Sasaki","sequence":"additional","affiliation":[{"name":"3Department of Biochemical Pathophysiology, Medical Research Laboratory, Institute for Integrated Research, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"PhD","given":"Nobuharu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"1Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8584-133X","authenticated-orcid":false,"suffix":"PhD","given":"Ryunosuke","family":"Ohkawa","sequence":"additional","affiliation":[{"name":"1Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"2026012211214884800_BSR-2025-3768R1","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1186\/s12872-024-04317-9","article-title":"Association between homocysteine levels and mortality in CVD: a cohort study based on NHANES database","volume":"24","author":"Liu","year":"2024","journal-title":"BMC Cardiovasc. 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