5730b8b3b625c3dda84075d9c249b83b pmc_29019935.pdf a80b6ee74f84dff158e9e63dd7a2ff8ad4518dd9 pmc_29019935.pdf Title: Cardiotoxic Effects of Short-Term Doxorubicin Administration: Involvement of Connexin 43 in Calcium Impairment Subject: The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy. C57BL/6j female mice were randomly divided in groups and injected with DOXO (2 or 10 mg/kg i.p.) for 1–3 or 7 days once every other day. Cardiac function was assessed by Echocardiography. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCAII) and phospholamban (PLB) expression were assessed by Western blot analysis, intracellular [Ca2+] were detected spectrofluorometrically by means of Fura-2 pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and localization was analyzed by Western blot and confirmed by immunofluorescence analysis. DOXO induces impairment in Ca2+ homeostasis, already evident after a single administration, and affects Cx43 expression and localization. Our data suggest that DOXO-induced alterations in Ca2+ homeostasis causes in the cells the induction of compensatory mechanisms until a certain threshold, above which cardiac injury is triggered. Keywords: connexin 43; doxorubicin; cardiotoxicity; calcium homeostasis; mitochondria Author: Michela Pecoraro, Antonio Rodríguez-Sinovas, Stefania Marzocco, Michele Ciccarelli, Guido Iaccarino, Aldo Pinto and Ada Popolo Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.17 CreationDate: Wed Oct 11 08:28:35 2017 CEST ModDate: Wed Oct 11 08:28:35 2017 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1987900 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ISHYIP+URWPalladioL-Ital Type 1 Custom yes yes no 112 0 UOOWXI+URWPalladioL-Bold Type 1 Custom yes yes no 113 0 WLENKM+VnURWPalladioL-Bold Type 1 Custom yes yes no 114 0 OXBKYU+TeXGyreAdventor-Bold Type 1 Custom yes yes no 115 0 KOOXDK+URWPalladioL-Roma Type 1 Custom yes yes no 116 0 VNRNEX+VnURWPalladioL Type 1 Custom yes yes no 117 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 122 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 123 0 DYUFJK+CMSY10 Type 1 Builtin yes yes no 159 0 NKXLQD+EURM10 Type 1 Builtin yes yes no 183 0 HLCGBJ+PalatinoLinotype CID TrueType Identity-H yes yes yes 191 0 HLCGBK+PalatinoLinotype TrueType WinAnsi yes yes no 192 0 HLCGEL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 193 0 HLCGKK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 194 0 HLCHEI+TimesNewRoman TrueType WinAnsi yes yes no 195 0 HLCGBK+PalatinoLinotype TrueType WinAnsi yes yes no 235 0 HLCGEL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 236 0 HLCGKK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 237 0 HLCHEI+TimesNewRoman TrueType WinAnsi yes yes no 238 0 HLCGBJ+PalatinoLinotype CID TrueType Identity-H yes yes yes 277 0 HLCGBK+PalatinoLinotype TrueType WinAnsi yes yes no 278 0 HLCGEL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 279 0 HLCGKK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 280 0 HLCHEI+TimesNewRoman TrueType WinAnsi yes yes no 281 0 java.lang.ClassCastException: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject cannot be cast to edu.harvard.hul.ois.jhove.module.pdf.PdfDictionary at edu.harvard.hul.ois.jhove.module.PdfModule.readDocCatalogDict(PdfModule.java:1284) at edu.harvard.hul.ois.jhove.module.PdfModule.parse(PdfModule.java:525) at edu.harvard.hul.ois.jhove.JhoveBase.processFile(JhoveBase.java:825) at edu.harvard.hul.ois.jhove.JhoveBase.process(JhoveBase.java:614) at edu.harvard.hul.ois.jhove.JhoveBase.dispatch(JhoveBase.java:465) at Jhove.main(Jhove.java:296) Jhove (Rel. 1.6, 2011-01-04) Date: 2019-02-14 17:49:20 CET RepresentationInformation: pmc_29019935.pdf ReportingModule: BYTESTREAM, Rel. 1.3 (2007-04-10) LastModified: 2018-02-08 07:46:11 CET Size: 1987900 Format: bytestream Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/octet-stream Checksum: 5542b5da Type: CRC32 Checksum: 5730b8b3b625c3dda84075d9c249b83b Type: MD5 Checksum: a80b6ee74f84dff158e9e63dd7a2ff8ad4518dd9 Type: SHA-1