Cardiotoxic Effects of Short-Term Doxorubicin Administration : Involvement of Connexin 43 in Calcium Impairment
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 18(2017), 10 vom: 11. Okt. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pecoraro, Michela [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 25.05.2018 Date Revised 12.04.2019 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms18102121 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM276889487 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM276889487 | ||
| 003 | DE-627 | ||
| 005 | 20231225012958.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms18102121 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0922.xml |
| 035 | |a (DE-627)NLM276889487 | ||
| 035 | |a (NLM)29019935 | ||
| 035 | |a (PII)E2121 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pecoraro, Michela |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cardiotoxic Effects of Short-Term Doxorubicin Administration |b Involvement of Connexin 43 in Calcium Impairment |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.05.2018 | ||
| 500 | |a Date Revised 12.04.2019 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a calcium homeostasis | |
| 650 | 4 | |a cardiotoxicity | |
| 650 | 4 | |a connexin 43 | |
| 650 | 4 | |a doxorubicin | |
| 650 | 4 | |a mitochondria | |
| 650 | 7 | |a Antibiotics, Antineoplastic |2 NLM | |
| 650 | 7 | |a Calcium-Binding Proteins |2 NLM | |
| 650 | 7 | |a Connexin 43 |2 NLM | |
| 650 | 7 | |a GJA1 protein, mouse |2 NLM | |
| 650 | 7 | |a phospholamban |2 NLM | |
| 650 | 7 | |a Doxorubicin |2 NLM | |
| 650 | 7 | |a 80168379AG |2 NLM | |
| 650 | 7 | |a Sarcoplasmic Reticulum Calcium-Transporting ATPases |2 NLM | |
| 650 | 7 | |a EC 3.6.3.8 |2 NLM | |
| 650 | 7 | |a Atp2a2 protein, mouse |2 NLM | |
| 650 | 7 | |a EC 7.2.2.10 |2 NLM | |
| 650 | 7 | |a Calcium |2 NLM | |
| 650 | 7 | |a SY7Q814VUP |2 NLM | |
| 700 | 1 | |a Rodríguez-Sinovas, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Marzocco, Stefania |e verfasserin |4 aut | |
| 700 | 1 | |a Ciccarelli, Michele |e verfasserin |4 aut | |
| 700 | 1 | |a Iaccarino, Guido |e verfasserin |4 aut | |
| 700 | 1 | |a Pinto, Aldo |e verfasserin |4 aut | |
| 700 | 1 | |a Popolo, Ada |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 18(2017), 10 vom: 11. Okt. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:18 |g year:2017 |g number:10 |g day:11 |g month:10 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms18102121 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 18 |j 2017 |e 10 |b 11 |c 10 | ||