Wang F, Seta Y, Baumgarten G, Engel D J, Sivasubramanian N, Mann D L
Winters Center for Heart Failure Research, Department of Medicine, Houston VA Medical Center,Baylor College of Medicine, Houston, TX 77030, USA.
Circulation. 2001 Mar 6;103(9):1296-302. doi: 10.1161/01.cir.103.9.1296.
Leukemia-inhibitory factor (LIF) is a member of the interleukin-6 family of cytokines that utilize gp130 as a common signaling component. In the present study, we examined the mechanisms that govern LIF expression and functional effects in the adult heart.
LIF mRNA and protein biosynthesis were examined in the adult feline heart after hemodynamic overloading ex vivo. Both LIF mRNA and protein expression were detected within 60 to 90 minutes after hemodynamic overloading. Studies in isolated adult cardiac myocytes showed that these cells synthesized both LIF mRNA and protein. The functional effects of LIF in the heart were demonstrated by studies that showed that LIF stimulation led to a significant increase in general protein synthesis and an increase in sarcomeric protein synthesis. Pretreatment with LIF also protected the cells against hypoxia/reoxygenation-induced cardiac myocyte apoptosis and cellular injury. Finally, LIF had no effect on isolated cardiac myocyte cell motion.
Hemodynamic overload is a sufficient stimulus for LIF expression in the adult mammalian heart. Given that LIF confers both hypertrophic and cytoprotective responses in adult cardiac myocytes, this study suggests that the expression of LIF within the heart may play an important role in mediating homeostatic responses within the myocardium.
白血病抑制因子（LIF）是白细胞介素-6细胞因子家族的成员，该家族细胞因子利用gp130作为共同的信号传导成分。在本研究中，我们研究了在成年心脏中调控LIF表达和功能效应的机制。
在体外血流动力学过载后，检测成年猫心脏中的LIF mRNA和蛋白质生物合成。血流动力学过载后60至90分钟内检测到LIF mRNA和蛋白质表达。对分离的成年心肌细胞的研究表明，这些细胞合成LIF mRNA和蛋白质。LIF在心脏中的功能效应通过研究得以证实，这些研究表明LIF刺激导致总蛋白合成显著增加以及肌节蛋白合成增加。用LIF预处理还可保护细胞免受缺氧/复氧诱导的心肌细胞凋亡和细胞损伤。最后，LIF对分离的心肌细胞运动没有影响。
血流动力学过载是成年哺乳动物心脏中LIF表达的充分刺激因素。鉴于LIF在成年心肌细胞中赋予肥大和细胞保护反应，本研究表明心脏内LIF的表达可能在介导心肌内的稳态反应中起重要作用。
