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Markers of autophagy are elevated in cardiac tissue following doxorubicin administration
Author(s) -
Kavazis Andreas N,
Smuder Ashley J,
Min Kisuk,
Powers Scott K
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1086.10
Subject(s) - doxorubicin , cardiotoxicity , autophagy , medicine , pharmacology , doxorubicin hydrochloride , saline , chemotherapy , biology , apoptosis , biochemistry
Doxorubicin is an antitumor agent used in cancer treatment, but its clinical use is limited due to cardiotoxicity. Although, numerous studies have investigated the signaling pathways responsible for doxorubicin‐induced cardiotoxicity, the role that the autophagy/lysosomal system plays in doxorubicin‐induced cardiac damage remains unknown. We hypothesized that systemic doxorubicin administration would result in increased activation of the autophagy system in the heart. To test this postulate, adult, male Sprague‐Dawley rats were randomly assigned to placebo or doxorubicin groups. Doxorubicin animals received doxorubicin hydrochloride (20 mg/kg body weight IP) 24 hours prior to sacrifice, whereas placebo groups received saline injections. Following treatment, hearts were excised and used for biochemical analyses. Doxorubicin administration resulted in increased cardiac levels of mRNA and protein abundance of key autophagy markers. Specifically, mRNA levels of beclin (+58%), ATG12 (+41%), and LC3 (+46%) were significantly (p<0.05) increased in the heart following doxorubicin administration. Also, protein levels of beclin (+32%), ATG12 (+47%), and ATG7 (+28%) were significantly (p<0.05) increased in heart muscle isolated from animals treated with doxorubicin. These findings suggest that increased autophagy is a contributing factor of doxorubicin‐induced cardiotoxicity.