{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:42:12Z","timestamp":1790786532385,"version":"4.1.0"},"reference-count":62,"publisher":"SAGE Publications","issue":"16","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    The discovery of methionine metabolism enzymes in the cell nucleus, together with their association with key nuclear processes, suggested a putative relationship between alterations in their subcellular distribution and disease.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    Using the rat model of\n                    <jats:sc>d<\/jats:sc>\n                    -galactosamine intoxication, severe changes in hepatic steady-state mRNA levels were found; the largest decreases corresponded to enzymes exhibiting the highest expression in normal tissue. Cytoplasmic protein levels, activities, and metabolite concentrations suffered more moderate changes following a similar trend. Interestingly, galactosamine treatment induced hepatic nuclear accumulation of methionine adenosyltransferase (MAT) \u03b11 and\n                    <jats:italic toggle=\"yes\">S<\/jats:italic>\n                    -adenosylhomocysteine hydrolase tetramers, their active assemblies. In fact, galactosamine-treated livers showed enhanced nuclear MAT activity. Acetaminophen (APAP) intoxication mimicked most galactosamine effects on hepatic MAT\u03b11, including accumulation of nuclear tetramers. H35 cells that overexpress tagged-MAT\u03b11 reproduced the subcellular distribution observed in liver, and the changes induced by galactosamine and APAP that were also observed upon glutathione depletion by buthionine sulfoximine. The H35 nuclear accumulation of tagged-MAT\u03b11 induced by these agents correlated with decreased glutathione reduced form\/glutathione oxidized form ratios and was prevented by\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -acetylcysteine (NAC) and glutathione ethyl ester. However, the changes in epigenetic modifications associated with tagged-MAT\u03b11 nuclear accumulation were only prevented by NAC in galactosamine-treated cells.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    Cytoplasmic and nuclear changes in proteins that regulate the methylation index follow opposite trends in acute liver injury, their nuclear accumulation showing potential as disease marker.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    Altogether these results demonstrate galactosamine- and APAP-induced nuclear accumulation of methionine metabolism enzymes as active oligomers and unveil the implication of redox-dependent mechanisms in the control of MAT\u03b11 subcellular distribution.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    20, 2541\u20132554.\n                  <\/jats:p>","DOI":"10.1089\/ars.2013.5342","type":"journal-article","created":{"date-parts":[[2013,10,14]],"date-time":"2013-10-14T08:31:03Z","timestamp":1381739463000},"page":"2541-2554","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Acute Liver Injury Induces Nucleocytoplasmic Redistribution of Hepatic Methionine Metabolism Enzymes"],"prefix":"10.1177","volume":"20","author":[{"given":"Miguel","family":"Delgado","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Garrido","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"P\u00e9rez-Miguelsanz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM)","place":["Spain"]},{"name":"Universidad Complutense de Madrid","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Partearroyo","sequence":"additional","affiliation":[{"name":"Universidad CEU San Pablo","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"P\u00e9rez-Sala","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas (CSIC)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Angeles","family":"Pajares","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM)","place":["Spain"]},{"name":"Molecular Hepatology Group","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,6,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)81245-4"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3010557"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.9.2499"},{"key":"e_1_3_3_5_2","first-page":"391","article-title":"Regulation of rat liver S-adenosylmethionine synthetase during septic shock: role of nitric oxide","volume":"25","author":"Avila MA","year":"1997","unstructured":"Avila MA, , Mingorance J, , Martinez-Chantar ML, , Casado M, , Martin-Sanz P, , Bosca L, , and Mato JM. 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