急性阿霉素治疗对肝脏蛋白质组赖氨酸乙酰化状态及凋亡环境的影响。
Effects of acute doxorubicin treatment on hepatic proteome lysine acetylation status and the apoptotic environment.
作者信息
Dirks-Naylor Amie J, Kouzi Samir A, Bero Joseph D, Tran Ngan Tk, Yang Sendra, Mabolo Raean
机构信息
Amie J Dirks-Naylor, Samir A Kouzi, Joseph D Bero, Ngan TK Tran, Sendra Yang, Raean Mabolo, School of Pharmacy, Wingate University, Wingate, NC 28174, United States.
出版信息
World J Biol Chem. 2014 Aug 26;5(3):377-86. doi: 10.4331/wjbc.v5.i3.377.
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 activation under these experimental conditions.
目的
确定阿霉素（Dox）是否会改变肝脏蛋白质组的乙酰化状态，以及乙酰化状态是否与凋亡环境相关。
方法
对6周龄雄性F344大鼠腹腔注射阿霉素（20mg/kg；Sigma，圣路易斯，密苏里州；n = 8）或氯化钠（0.9%；n = 7）。用阿霉素或生理盐水处理动物后，所有动物禁食直至24小时后处死。
结果
阿霉素处理降低了蛋白质组赖氨酸乙酰化，这可能是由于组蛋白乙酰转移酶活性降低所致。蛋白质组去乙酰化可能与促凋亡环境无关。阿霉素未增加半胱天冬酶-9、-8或-3的激活，也未增加聚（二磷酸腺苷核糖）聚合酶-1的切割。然而，阿霉素确实刺激了半胱天冬酶-12的激活，但它可能在凋亡诱导中不起作用。
结论
在这些实验条件下，阿霉素的早期作用涉及肝脏蛋白质组赖氨酸去乙酰化和半胱天冬酶-12激活。
Zotero 插件