School of Pharmacy, Wingate University, 515 N. Main Street, Wingate, NC, 28174, USA,
J Cachexia Sarcopenia Muscle. 2013 Sep;4(3):239-43. doi: 10.1007/s13539-013-0104-z. Epub 2013 Mar 26.
Doxorubicin treatment is known to cause muscular weakness. However, the cellular mechanisms have not been elucidated. We aimed to determine the effects of acute doxorubicin treatment on proteome lysine acetylation status, an indication of the apoptotic and inflammatory environment, and the expression and activation of various apical caspases involved in the initiation of apoptosis.
Six-week-old male F344 rats were injected intraperitoneally with 20 mg/kg of doxorubicin or saline. Once the treatment was administered, both groups of animals were fasted with no food or water until sacrifice 24 h posttreatment.
Doxorubicin treatment affected neither the proteome lysine acetylation status nor the expression of sirtuin 1, sirtuin 3, SOD1, or SOD2 in soleus of fasted animals. Doxorubicin treatment also did not affect the expression or activation of procaspase-1, procaspase-8, procaspase-9, or procaspase-12.
We suggest that doxorubicin does not exert a direct effect on these catabolic parameters in skeletal muscle in vivo.
多柔比星治疗已知会导致肌肉无力。然而,其细胞机制尚未阐明。我们旨在确定急性多柔比星治疗对蛋白质组赖氨酸乙酰化状态的影响,这是凋亡和炎症环境的一个指标,以及涉及凋亡起始的各种顶端半胱氨酸天冬氨酸蛋白酶的表达和激活。
将 6 周龄雄性 F344 大鼠腹膜内注射 20mg/kg 的多柔比星或生理盐水。一旦进行了治疗,两组动物均禁食,在治疗后 24 小时处死前,不给食物或水。
多柔比星治疗既不影响禁食动物的骨骼肌蛋白质组赖氨酸乙酰化状态,也不影响沉默调节蛋白 1、沉默调节蛋白 3、SOD1 或 SOD2 的表达。多柔比星治疗也不影响前胱天蛋白酶-1、前胱天蛋白酶-8、前胱天蛋白酶-9 或前胱天蛋白酶-12 的表达或激活。
我们认为,多柔比星在体内对骨骼肌的这些分解代谢参数没有直接作用。