{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:59:09Z","timestamp":1791331149263,"version":"4.3.1"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,2,9]],"date-time":"2009-02-09T00:00:00Z","timestamp":1234137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004569","name":"Ministerstwo Nauki i Szkolnictwa Wy\u017cszego","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Genetic disorders of homocysteine (Hcy) or folate metabolism or high\u2010methionine diets elevate plasma Hcy and its atherogenic metabolite Hcy\u2010thiolac\u2010tone. In humans, severe hyperhomocysteinemia due to genetic alterations in cystathionine \u03c2\u2010synthase\n                    <jats:italic>(Cbs)<\/jats:italic>\n                    or methylenetetrahydrofolate reductase\n                    <jats:italic>(Mthfr)<\/jats:italic>\n                    results in neurological abnormalities and premature death from vascular complications. In mouse models, dietary or genetic hyperhomocysteinemia results in liver or brain pathological changes and accelerates atherosclerosis. Hcy\u2010thiolactone has the ability to form isopeptide bonds with protein lysine residues, which generates modified proteins (A\u2010Hcy\u2010protein) with autoimmunogenic and prothrombotic properties. Our aim was to determine how\n                    <jats:italic>A<\/jats:italic>\n                    \u2013Hcy\u2010protein levels are affected by genetic or nutritional disorders in Hcy or folate metabolism in mice. We found that plasma A\u2010Hcy\u2010protein was elevated 10\u2010fold in mice fed a high\u2010methionine diet compared with the animals fed a normal commercial diet. We also found that inactivation of\n                    <jats:italic>Cbs, Mthfr<\/jats:italic>\n                    , or the proton\u2010coupled folate transporter\n                    <jats:italic>(Pcft)<\/jats:italic>\n                    gene resulted in a 10\u2010to 30\u2010fold increase in plasma or serum AHcy\u2010protein levels. Liver AHcy\u2010protein was elevated 3.4\u2010fold in severely and 11\u2010fold in extremely hyperhomocysteinemic Cbs\u2010deficient mice, 3.6\u2010fold in severely hyperhomocysteinemic\n                    <jats:italic>Pcft<\/jats:italic>\n                    mice, but was not elevated in mildly hyperhomocysteinemic Mthfr\u2010deficient animals, suggesting that mice have a capacity to prevent accumulation of A\u2010Hcy\u2010protein in their organs. These findings provide evidence that\n                    <jats:italic>A<\/jats:italic>\n                    \u2010Hcy\u2010protein is an important metabolite associated with Hcy pathophysiology in the mouse.\u2014Jakubowski, H.,Peria\u2010Kajan, J., Finnell, R.H., Cabrera, R.M., Wang, H., Gupta, S., Kruger, W.D., Kraus, J.P., Shih, D.M. Genetic or nutritional disorders in homocysteine or folate metabolism increase protein A\u2010homocysteinylation in mice.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    23, 1721\u20131727 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-127548","type":"journal-article","created":{"date-parts":[[2009,2,9]],"date-time":"2009-02-09T20:45:07Z","timestamp":1234212307000},"page":"1721-1727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Genetic or nutritional disorders in homocysteine or folate metabolism increase protein\n                    <i>N<\/i>\n                    \u2010homocysteinylation in mice"],"prefix":"10.1096","volume":"23","author":[{"given":"Hieronim","family":"Jakubowski","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics New Jersey Medical School University of Medicine and Dentistry of New Jersey International Center for Public Health Newark New Jersey USA"},{"name":"Department of Biochemistry and Biotechnology University of Life Sciences Pozna Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Per\u0142a-Kaj\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics New Jersey Medical School University of Medicine and Dentistry of New Jersey International Center for Public Health Newark New Jersey USA"},{"name":"Department of Biochemistry and Biotechnology University of Life Sciences Pozna Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Finnell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics New Jersey Medical School University of Medicine and Dentistry of New Jersey International Center for Public Health Newark New Jersey USA"},{"name":"Texas Institute for Genomic Medicine Institute of Biosciences and Technology The Texas A&amp;M University System Health Science Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Texas Institute for Genomic Medicine Institute of Biosciences and Technology The Texas A&amp;M University System Health Science Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Temple University School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sapna","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Population Fox Chase Cancer Center Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren D.","family":"Kruger","sequence":"additional","affiliation":[{"name":"Division of Population Fox Chase Cancer Center Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan P.","family":"Kraus","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado School of Medicine Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California Los Angeles Medical School Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,9]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"2007","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Mudd S.H.","year":"2001"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)81283-6"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.11.2983S"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3204-7"},{"key":"e_1_2_6_6_1","first-page":"384","volume-title":"The Aminoacyl-tRNA Synthetases","author":"Jakubowski H.","year":"2005"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)67504-6"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7435com"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.6.1741S"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.1.45"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.2.377S"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev.med.60.041807.123308","article-title":"The treatment of hyper-homocysteinemia","volume":"60","author":"Maron B.A.","year":"2008","journal-title":"Annu. 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