{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:55:53Z","timestamp":1784231753850,"version":"3.55.0"},"reference-count":45,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T00:00:00Z","timestamp":1546473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T00:00:00Z","timestamp":1546473600000},"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":[[2019,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      Human \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      -microglobulin (A1M) is an endogenous reductase and radical- and heme-binding protein with physiological antioxidant protective functions. Recombinant human A1M (rA1M) has been shown to have therapeutic properties in animal models of preeclampsia, a pregnancy disease associated with oxidative stress. Recombinant A1M, however, lacks glycosylation, and shows lower solubility and stability than A1M purified from human plasma. The aims of this work were to (i) use site-directed mutagenesis to improve the physicochemical properties of rA1M, (ii) demonstrate that the physicochemically improved rA1M displays full\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      cell protective effects as recombinant wild-type A1M (rA1M-wt), and (iii) show its therapeutic potential\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      against acute kidney injury (AKI), another disease associated with oxidative stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A novel recombinant A1M-variant (rA1M-035) with three amino acid substitutions was constructed, successfully expressed, and purified. rA1M-035 had improved solubility and stability compared with rA1M-wt, and showed intact\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      heme-binding, reductase, antioxidation, and cell protective activities. Both rA1M-035 and rA1M-wt showed, for the first time, potential\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      protective effects on kidneys using a mouse rhabdomyolysis glycerol injection model of AKI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>\n                      A novel recombinant A1M-variant, rA1M-035, was engineered. This protein showed improved solubility and stability compared with rA1M-wt, full\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      functional activity, and potential protection against AKI in an\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      rhabdomyolysis mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The new rA1M-035 is a better drug candidate than rA1M-wt for treatment of AKI and preeclampsia in human patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2017.7181","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T01:42:17Z","timestamp":1519350137000},"page":"489-504","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["rA1M-035, a Physicochemically Improved Human Recombinant \u03b1\n                    <sub>1<\/sub>\n                    -Microglobulin, Has Therapeutic Effects in Rhabdomyolysis-Induced Acute Kidney Injury"],"prefix":"10.1177","volume":"30","author":[{"given":"Bo","family":"\u00c5kerstr\u00f6m","sequence":"first","affiliation":[{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Rosenl\u00f6f","sequence":"additional","affiliation":[{"name":"A1M Pharma AB","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneli","family":"H\u00e4gerwall","sequence":"additional","affiliation":[{"name":"A1M Pharma AB","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigurbj\u00f6rg","family":"Rutardottir","sequence":"additional","affiliation":[{"name":"A1M Pharma AB","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Ahlstedt","sequence":"additional","affiliation":[{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Johansson","sequence":"additional","affiliation":[{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Erlandsson","sequence":"additional","affiliation":[{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Allhorn","sequence":"additional","affiliation":[{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Gram","sequence":"additional","affiliation":[{"name":"Lund University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,1,3]]},"reference":[{"key":"e_1_3_3_2_2","first-page":"333","article-title":"Biodistribution and pharmacokinetics of recombinant \u03b11-microglobulin and its potential use in radioprotection of kidneys","volume":"5","author":"Ahlstedt J","year":"2015","unstructured":"Ahlstedt J, , Tran TA, , Strand F, , Holmqvist B, , Strand S-E, , Gram M, , and \u00c5kerstr\u00f6m B. 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