{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:53:37Z","timestamp":1790038417000,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T00:00:00Z","timestamp":1559088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Modern diagnostic strategies for early recognition of cancer therapeutics-related cardiac dysfunction involve cardiac troponins measurement. Still, the role of other markers of cardiotoxicity is still unclear. The present study was designed to investigate dynamics of response of human cardiomyocytes derived from induced pluripotent stem cells (hiPCS-CMs) to doxorubicin with the special emphasis on their morphological changes in relation to expression and organization of troponins. The hiPCS-CMs were treated with doxorubicin concentrations (1 and 0.3 \u00b5M) for 48 h and followed for next up to 6 days. Exposure of hiPCS-CMs to 1 \u00b5M doxorubicininduced suppression of both cardiac troponin T (cTnT) and cardiac troponin I (cTnI) gene expression. Conversely, lower 0.3 \u00b5M doxorubicin concentration produced no significant changes in the expression of aforementioned genes. However, the intracellular topography, arrangement, and abundance of cardiac troponin proteins markedly changed after both doxorubicin concentrations. In particular, at 48 h of treatment, both cTnT and cTnI bundles started to reorganize, with some of them forming compacted shapes extending outwards and protruding outside the cells. At later intervals (72 h and onwards), the whole troponin network collapsed and became highly disorganized following, to some degree, overall changes in the cellular shape. Moreover, membrane permeability of cardiomyocytes was increased, and intracellular mitochondrial network rearranged and hypofunctional. Together, our results demonstrate complex effects of clinically relevant doxorubicin concentrations on hiPCS-CM cells including changes in cTnT and cTnI, but also in other cellular compartments contributing to the overall cytotoxicity of this class of cytostatics.<\/jats:p>","DOI":"10.3390\/ijms20112638","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T11:31:28Z","timestamp":1559129488000},"page":"2638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Cardiac Troponins are Among Targets of Doxorubicin-Induced Cardiotoxicity in hiPCS-CMs"],"prefix":"10.3390","volume":"20","author":[{"given":"Michaela","family":"Adamcova","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Simkova 870, 500 03 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Skarkova","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Zborovsk\u00e1 2089, 500 03 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitka","family":"Seifertova","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Zborovsk\u00e1 2089, 500 03 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9526-3174","authenticated-orcid":false,"given":"Emil","family":"Rudolf","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Zborovsk\u00e1 2089, 500 03 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1093\/eurheartj\/ehs181","article-title":"Cancer drugs and the heart: Importance and management","volume":"34","author":"Suter","year":"2013","journal-title":"Eur. 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