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The mechanisms underlying poor amputation stump healing in the setting of diabetes are not understood.\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetylcysteine (NAC) is known to promote endothelial cell function and angiogenesis and may have therapeutic benefits in the setting of diabetes. We tested the hypothesis that NAC alters the vascular milieu to improve healing of amputation stumps in diabetes using a novel\n                    <jats:italic>in vivo<\/jats:italic>\n                    murine hindlimb ischemia\u2010amputation model. Amputation stump tissue perfusion and healing were evaluated in C57BL\/6J adult mice with streptozotocin\u2010induced diabetes. Compared with controls, mice treated with daily NAC demonstrated improved postamputation stump healing, perfusion, adductor muscle neovascularization, and decreased muscle fiber damage. Additionally, NAC stimulated HUVEC migration and proliferation in a phospholipase C \u03b2\u2013dependent fashion and decreased G\u03b1q palmitoylation. Similarly, NAC treatment also decreased G\u03b1q palmitoylation in ischemic and nonischemic hindlimbs\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In summary, we demonstrate that NAC accelerates healing of amputation stumps in the setting of diabetes and ischemia. The underlying mechanism appears to involve a previously unrecognized effect of NAC on G\u03b1q palmitoylation and phospholipase C \u03b2\u2013mediated signaling in endothelial cells.\u2014Zayed, M. A., Wei, X., Park, K., Belaygorod, L., Naim, U., Harvey, J., Yin, L., Blumer, K., Semenkovich,\n                    <jats:italic>C. F.<\/jats:italic>\n                    N\u2010acetylcysteine accelerates amputation stump healing in the setting of diabetes. FASEB J. 31, 2686\u20132695 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201601348r","type":"journal-article","created":{"date-parts":[[2017,3,9]],"date-time":"2017-03-09T21:00:31Z","timestamp":1489093231000},"page":"2686-2695","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["<i>N<\/i>\n                    \u2010acetylcysteine accelerates amputation stump healing in the setting of diabetes"],"prefix":"10.1096","volume":"31","author":[{"given":"Mohamed A.","family":"Zayed","sequence":"first","affiliation":[{"name":"Section of Vascular Surgery Department of Surgery"},{"name":"Department of Surgery St. Louis Veterans Affairs Health Care System, St. Louis  Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiachao","family":"Wei","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Metabolism, and Lipid Research Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoung\u2010mi","family":"Park","sequence":"additional","affiliation":[{"name":"Section of Vascular Surgery Department of Surgery"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larisa","family":"Belaygorod","sequence":"additional","affiliation":[{"name":"Section of Vascular Surgery Department of Surgery"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uzma","family":"Naim","sequence":"additional","affiliation":[{"name":"Section of Vascular Surgery Department of Surgery"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Metabolism, and Lipid Research Department of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendall","family":"Blumer","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clay F.","family":"Semenkovich","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Metabolism, and Lipid Research Department of Medicine"},{"name":"Department of Cell Biology and Physiology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2013.11.008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310799"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/03093648009164567"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-481X.2007.00313.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2009.00543.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2004.06.072"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.04.016"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)90612-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2015.04.017"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.05.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.12.2398"},{"key":"e_1_2_8_13_1","first-page":"642","article-title":"Increase in glucose consumption by acetylcysteine during hyperglycemic clamp: a study with healthy volunteers","volume":"42","author":"Ammon H. 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