{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:59:19Z","timestamp":1792180759410,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T00:00:00Z","timestamp":1524096000000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["5172027"],"award-info":[{"award-number":["5172027"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>24\u2010dehydrocholesterol reductase (Dhcr24) catalyzes the last step of cholesterol biosynthesis, which is required for normal development and anti\u2010apoptotic activities of tissues. We found that Dhcr24 expression decreased in the <jats:styled-content style=\"fixed-case\">cTnT<jats:sup>R<\/jats:sup><\/jats:styled-content><jats:sup>141W<\/jats:sup> dilated cardiomyopathy (<jats:styled-content style=\"fixed-case\">DCM<\/jats:styled-content>) transgenic mice. Therefore, we tested whether rescued expression of Dhcr24 could prevent the development of <jats:styled-content style=\"fixed-case\">DCM<\/jats:styled-content> and its possible mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Heart tissue specific transgenic overexpression mice of Dhcr24 was generated, then was crossed to <jats:styled-content style=\"fixed-case\">cTnT<jats:sup>R<\/jats:sup><\/jats:styled-content><jats:sup>141W<\/jats:sup> mouse to obtain the double transgenic mouse (<jats:styled-content style=\"fixed-case\">DTG<\/jats:styled-content>). The phenotypes were demonstrated by the survival, cardiac geometry and function analysis, as well as microstructural and ultrastructural observations based on echocardiography and histology examination. The pathway and apoptosis were analysed by western blotting and <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content> assay in\u00a0vivo and in\u00a0vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We find that Dhcr24 decreased in hearts tissues of <jats:styled-content style=\"fixed-case\">cTnT<jats:sup>R<\/jats:sup><\/jats:styled-content><jats:sup>141W<\/jats:sup> and <jats:styled-content style=\"fixed-case\">LMNA<jats:sup>E<\/jats:sup><\/jats:styled-content><jats:sup>82K<\/jats:sup> <jats:styled-content style=\"fixed-case\">DCM<\/jats:styled-content> mice. The transgenic overexpression of Dhcr24 significantly improves <jats:styled-content style=\"fixed-case\">DCM<\/jats:styled-content> phenotypes in <jats:styled-content style=\"fixed-case\">cTnT<jats:sup>R<\/jats:sup><\/jats:styled-content><jats:sup>141W<\/jats:sup> mice, and activates <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt\/<jats:styled-content style=\"fixed-case\">HKII<\/jats:styled-content> pathway, followed by a reduction of the translocation of Bax and release of cytochrome <jats:italic>c<\/jats:italic>, caspase\u20109 and caspase\u20103 activation and myocyte apoptosis. Knockdown the expression of Dhcr24 reduces the activation of <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt\/<jats:styled-content style=\"fixed-case\">HKII<\/jats:styled-content> pathway and inhibition of the mitochondrial\u2010dependent apoptosis. The anti\u2010apoptotic effect of Dhcr24 could be completely removed by the inhibition of <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K pathway and partly removed by the <jats:styled-content style=\"fixed-case\">HKII<\/jats:styled-content> inhibitor in H9c2 cell line.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Compensatory expression of Dhcr24 protect against <jats:styled-content style=\"fixed-case\">DCM<\/jats:styled-content> through activated <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt\/<jats:styled-content style=\"fixed-case\">HKII<\/jats:styled-content> pathway and reduce Bax translocation. This is the first investigation for the molecular mechanism of Dhcr24 participate in development of <jats:styled-content style=\"fixed-case\">DCM<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12007","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T20:12:49Z","timestamp":1524168769000},"page":"40-52","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Dhcr24 activates the <scp>PI<\/scp>3K\/Akt\/<scp>HKII<\/scp> pathway and protects against dilated cardiomyopathy in mice"],"prefix":"10.1002","volume":"1","author":[{"given":"Wei","family":"Dong","sequence":"first","affiliation":[{"name":"Key Laboratory of Human Disease Comparative Medicine NHFPC Institute of Laboratory Animal Science Chinese Academy of Medical Sciences &amp; Comparative Medical Center Peking Union Medical College Beijing 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