{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T14:06:49Z","timestamp":1773238009668,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,11,10]],"date-time":"2005-11-10T00:00:00Z","timestamp":1131580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Motil. Cytoskeleton"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Corneal endothelial cells respond to a circular freeze wound by undergoing actin cytoskeletal reorganization that is mainly characterized by the disappearance of circumferential microfilament bundles (CMBs) and the subsequent appearance of distinct stress fibers. This cytoskeletal rearrangement is associated with changes in cell shape as migrating cells lose their polyhedral appearance, spread out, and assume a stellate morphology with cell processes extending outward into the injured area. We report here that in the presence of low concentrations (0.01\u20130.l mM) of the anti\u2010metabolite 5\u2010fluorouracil (5\u2010FU), characteristic actin organization becomes disrupted and migrating cells do not display elongated processes typical of control tissues and translocation into the injury zone is retarded, but not inhibited. Rhodamine phalloidin staining revealed no evidence of stress fiber formation. A higher concentration of 5\u2010FU (1.0 mM) not only prevented formation of discernible stress fibers but also resulted in a more restricted cell movement during wound repair. That this was not a cytotoxic effect was demonstrated by transferring tissues back into standard medium allowing endothelia to reinitiate migration and undergo complete wound healing by 72 h post\u2010transfer. Overnight incubation of endothelia in 4 \u03bcM phallacidin resulted in limited CMB disruption the extent of which was dependent on the 5\u2010FU concentration. The effects of 5\u2010FU on the actin cytoskeleton are reversible and by 24 h after placing treated endothelia into medium without 5\u2010FU, actin begins to become re\u2010established and by 48 h microfilament patterns in the tissue resemble those of non\u2010treated endothelia. Similarly, when noninjured tissues are cultured in the presence of 5\u2010FU for 24 h, subsequently injured and returned to standard medium, they exhibit no stress fibers when observed at 24 h post\u2010wounding. However, by 48 h post\u2010injury these cells now display stress fibers and extend processes into the wound area. Biochemical studies on isolated muscle actin demonstrated that actin polymerization is unaffected in the presence of either 0.01 or 1 mM 5\u2010FU as determined by the F\u2010actin sedimentation and falling ball viscosity techniques. Thus, the mechanism(s) by which 5\u2010FU exerts its actions on the actin cytoskeleton appears to be one of an indirect nature. Cell Motil. Cytoskeleton 62:244\u2013258, 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cm.20099","type":"journal-article","created":{"date-parts":[[2005,11,16]],"date-time":"2005-11-16T21:53:01Z","timestamp":1132177981000},"page":"244-258","source":"Crossref","is-referenced-by-count":13,"title":["5\u2010fluorouracil interferes with actin organization, stress fiber formation and cell migration in corneal endothelial cells during wound repair along the natural basement membrane"],"prefix":"10.1002","volume":"62","author":[{"given":"Sheldon R.","family":"Gordon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Climie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne L.","family":"Hitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,10]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"1115","article-title":"The spatial organization of corneal endothelial cytoskeletal proteins and their relationship to the apical junctional complex","volume":"36","author":"Barry PA","year":"1995","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(02)00059-9"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)67474-5"},{"key":"e_1_2_1_5_1","first-page":"308","article-title":"Cytotoxicity and the inhibition of ribosomal RNA processing in human colon carcinoma cells","volume":"27","author":"Cohen MB","year":"1985","journal-title":"Mol Pharmacol"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1016\/S0021-9258(18)89465-0","article-title":"Effects of 5\u2010fluorouracil on dihydrofolate reductase and dihydrofolate reductase mRNA from methotrexate\u2010resistant KB cells","volume":"260","author":"Dolnick BJ","year":"1985","journal-title":"J Biol Chem"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.88.2.388"},{"key":"e_1_2_1_8_1","first-page":"393","article-title":"Actin in wound\u2010healing of rabbit corneal endothelium. 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