{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:50:52Z","timestamp":1790754652800,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              Globotriaosylceramide (Gb3) induces K\n              <jats:sub>Ca<\/jats:sub>\n              3.1 downregulation in Fabry disease (FD). We investigated whether Gb3 induces K\n              <jats:sub>Ca<\/jats:sub>\n              3.1 endocytosis and degradation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              K\n              <jats:sub>Ca<\/jats:sub>\n              3.1, especially plasma membrane\u2013localized K\n              <jats:sub>Ca<\/jats:sub>\n              3.1, was downregulated in both Gb3-treated mouse aortic endothelial cells (MAECs) and human umbilical vein endothelial cells. Gb3-induced K\n              <jats:sub>Ca<\/jats:sub>\n              3.1 downregulation was prevented by lysosomal inhibitors but not by a proteosomal inhibitor. Endoplasmic reticulum stress\u2013inducing agents did not induce K\n              <jats:sub>Ca<\/jats:sub>\n              3.1 downregulation. Gb3 upregulated the protein levels of early endosome antigen 1 and lysosomal-associated membrane protein 2 in MAECs. Compared with MAECs from age-matched wild-type mice, those from aged \u03b1-galactosidase A (Gla)-knockout mice, an animal model of FD, showed downregulated K\n              <jats:sub>Ca<\/jats:sub>\n              3.1 expression and upregulated early endosome antigen 1 and lysosomal-associated membrane protein 2 expression. In contrast, no significant difference was found in early endosome antigen 1 and lysosomal-associated membrane protein 2 expression between young Gla-knockout and wild-type MAECs. In aged Gla-knockout MAECs, clathrin was translocated close to the cell border and clathrin knockdown recovered K\n              <jats:sub>Ca<\/jats:sub>\n              3.1 expression. Rab5, an effector of early endosome antigen 1, was upregulated, and Rab5 knockdown restored K\n              <jats:sub>Ca<\/jats:sub>\n              3.1 expression, the current, and endothelium-dependent relaxation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\n              \u2014Gb3 accelerates the endocytosis and lysosomal degradation of endothelial K\n              <jats:sub>Ca<\/jats:sub>\n              3.1 via a clathrin-dependent process, leading to endothelial dysfunction in FD.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.113.302200","type":"journal-article","created":{"date-parts":[[2013,10,25]],"date-time":"2013-10-25T08:30:36Z","timestamp":1382689836000},"page":"81-89","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Globotriaosylceramide Induces Lysosomal Degradation of Endothelial K\n            <sub>Ca<\/sub>\n            3.1 in Fabry Disease"],"prefix":"10.1161","volume":"34","author":[{"given":"Shinkyu","family":"Choi","sequence":"first","affiliation":[{"name":"From the Departments of Physiology (S.C., J.A.K., H.-Y.N., S.-E.C., S.P., S.H.S.) and Biochemistry (S.-C.J.), Medical School, Ewha Womans University, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Aee","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology (S.C., J.A.K., H.-Y.N., S.-E.C., S.P., S.H.S.) and Biochemistry (S.-C.J.), Medical School, Ewha Womans University, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Young","family":"Na","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology (S.C., J.A.K., H.-Y.N., S.-E.C., S.P., S.H.S.) and Biochemistry (S.-C.J.), Medical School, Ewha Womans University, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Eun","family":"Cho","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology (S.C., J.A.K., H.-Y.N., S.-E.C., S.P., S.H.S.) and Biochemistry (S.-C.J.), Medical School, Ewha Womans University, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seonghee","family":"Park","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology (S.C., J.A.K., H.-Y.N., S.-E.C., S.P., S.H.S.) and Biochemistry (S.-C.J.), Medical School, Ewha Womans University, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Chul","family":"Jung","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology (S.C., J.A.K., H.-Y.N., S.-E.C., S.P., S.H.S.) and Biochemistry (S.-C.J.), Medical School, Ewha Womans University, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Hyo","family":"Suh","sequence":"additional","affiliation":[{"name":"From the Departments of Physiology (S.C., J.A.K., H.-Y.N., S.-E.C., S.P., S.H.S.) and Biochemistry (S.-C.J.), Medical School, Ewha Womans University, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61589-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcq117"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000238377.08219.0c"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.846634"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq333"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.12.009"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0843-y"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.11.003"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.066902"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.086553"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00120.2010"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0438-5"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209235"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.203901"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.699"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/17618"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90120-5"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.034546"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199102073240607"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22776"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70018-1"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90316-Q"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.6.3745"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-187005"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-0563-2"}],"container-title":["Arteriosclerosis, 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