{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T22:34:15Z","timestamp":1770417255563,"version":"3.49.0"},"reference-count":76,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T00:00:00Z","timestamp":1541635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["6793"],"award-info":[{"award-number":["6793"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>The wood frog, <jats:styled-content style=\"fixed-case\"><jats:italic>Lithobates sylvaticus<\/jats:italic><\/jats:styled-content> (also known as <jats:styled-content style=\"fixed-case\"><jats:italic>Rana sylvatica<\/jats:italic><\/jats:styled-content>), is used for studying natural freeze tolerance. These animals convert 65% to 70% of their total body water into extracellular ice and survive freezing for weeks in winter. Freezing interrupts oxygen delivery to organs; thus, wood frogs limit their ATP usage by depressing their metabolism and redirecting the available energy only to prosurvival processes. Here, we studied the nuclear factor of activated T cell (NFAT) transcription factor family in response to 24\u2010hour anoxia, and 4\u2010hour aerobic recovery in liver and skeletal muscle. Protein expression levels of NFATc1\u2010c4, calcineurin A and glycogen synthase kinase 3\u03b2 (NFAT regulators), osteopontin, and atrial natriuretic peptide (ANP) (targets of NFATc3 and NFATc4, respectively) were measured by immunoblotting, and the DNA\u2010binding activities of NFATc1\u2010c4 were measured by DNA\u2010protein interaction ELISAs. Results show that NFATc4, calcineurin, and ANP protein expression as well as NFATc4 DNA binding increased during anoxia in liver where calcineurin and ANP protein levels and NFATc4 DNA binding remaining high after aerobic recovery. Anoxia caused a significant increase in NFATc3 protein expression but not DNA\u2010binding activity in muscle. Our results show that anoxia can increase NFATc4 transcriptional activity in liver, leading to the increase in expression of cytoprotective genes in the wood frog. Understanding the molecular mechanisms involved in mediating survival under anoxia\/reoxygenation conditions in a naturally stress\u2010tolerant model, such as the wood frog, provides insightful information on the prosurvival regulatory mechanisms involved in combating stress. This information will also further our understanding of metabolic rate depression and answer the question of how frogs tolerate prolonged periods of oxygen deprivation and resume to full function upon recovery without facing any detrimental side effects as other animals would.<\/jats:p>","DOI":"10.1002\/cbf.3362","type":"journal-article","created":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T21:37:46Z","timestamp":1541713066000},"page":"420-430","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of anoxic exposure on the nuclear factor of activated T cell (NFAT) transcription factors in the stress\u2010tolerant wood frog"],"prefix":"10.1002","volume":"36","author":[{"given":"Rasha","family":"Al\u2010Attar","sequence":"first","affiliation":[{"name":"Institude of Biochemistry and Department of Biology Carleton University  Ottawa 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