Effects of acute doxorubicin treatment on hepatic proteome lysine acetylation status and the apoptotic environment

• 作者: Amie J Dirks-Naylor Joseph D Bero Ngan TK Tran Raean Mabolo Samir A Kouzi Sendra Yang
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: SIRTUIN 1 SIRTUIN 3 Caspase Apoptosis ACETYLATION HISTONE DEACETYLASE HISTONE ACETYLTRANSFERASE
• 年，卷（期）: 2014,（3）
• 页码范围: 377-386
• 页数: 10页
• 分类号: R575

摘要

AIM: To determine if doxorubicin(Dox) alters hepatic proteome acetylation status and if acetylation status was associated with an apoptotic environment. METHODS: Doxorubicin(20 mg/kg; Sigma, Saint Louis, MO; n = 8) or NaCl(0.9%; n = 7) was administered as an intraperitoneal injection to male F344 rats, 6-wk of age. Once animals were treated with Dox or saline, all animals were fasted until sacrifice 24 h later. RESULTS: Dox treatment decreased proteome lysine acetylation likely due to a decrease in histone acetyltransferase activity. Proteome deacetylation may likely not be associated with a proapoptotic environment. Dox did not increase caspase-9,-8, or-3 activation nor poly(adenosine diphosphate-ribose) polymerase-1 cleavage. Dox did stimulate caspase-12 activation, however, it likely did not play a role in apoptosis induction. CONCLUSION: Early effects of Dox involve hepatic proteome lysine deacetylation and caspase-12 activa-tion under these experimental conditions.