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Acute doxorubicin treatment induces proteome lysine deacetylation, with no change in sirtuin expression, in the heart and liver of fasted animals
Author(s) -
DirksNaylor Amie Jeanette,
Bero Joseph D.,
Yang Sendra,
Mabolo Raean,
Tran Ngan T.K.,
Kouzi Samir A.
Publication year - 2013
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.27.1_supplement.1179.7
Subject(s) - sirtuin , lysine , acetylation , apoptosis , sirtuin 1 , proteome , pharmacology , toxicity , doxorubicin , oxidative stress , chemistry , biochemistry , biology , downregulation and upregulation , medicine , chemotherapy , gene , amino acid , organic chemistry
Doxorubicin (DOX) is an effective chemotherapeutic agent, but with known toxicity which limits its lifetime dosage. In various experimental models, cellular stress has been shown to alter proteome lysine acetylation status, causing deacetylation which was associated with a pro‐apoptotic environment. The effects of DOX on proteome lysine acetylation status and expression of related sirtuins is unknown, thus we aimed to determine these effects in heart and liver of treated animals. Male F344 rats were injected IP with 20 mg/kg of DOX or saline. Once treated, all animals were fasted with no food or water until sacrifice 24 hours later. DOX treatment caused significant deacetylation in heart and liver. DOX did not affect the expression of sirtuin 1 or 3 in either tissue. Western analysis of sirtuin 1 revealed a prominent band of ~40kDa in liver, but not heart. Further, DOX treatment increased the content of this species. It has been reported in chondrocytes that sirtuin 1 can be cleaved into a ~75kDa protein which can bind to cytochrome c and inhibit apoptosis. The ~40 kDa fragment may be the remaining cleaved fragment detected by the antibody used. In conclusion, DOX induces proteome lysine deacetylation, which may be due to other deacetylases. Further, liver, but not heart, may be another tissue type that produces a 75 kDa product of sirtuin 1 as a mechanism to protect against apoptosis and is responsive to DOX treatment.