کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2192102 | 1097881 | 2007 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: SHP2-mediated signaling cascade through gp130 is essential for LIF-dependent ICaL, [Ca2+]i transient, and APD increase in cardiomyocytes SHP2-mediated signaling cascade through gp130 is essential for LIF-dependent ICaL, [Ca2+]i transient, and APD increase in cardiomyocytes](/preview/png/2192102.png)
Leukemia inhibitory factor (LIF), a cardiac hypertrophic cytokine, increases L-type Ca2+ current (ICaL) via ERK-dependent and PKA-independent phosphorylation of serine 1829 in the Cav1.2 subunit. The signaling cascade through gp130 is involved in this augmentation. However, there are two major cascades downstream of gp130, i.e. JAK/STAT3 and SHP2/ERK. In this study, we attempted to clarify which of these two cascades plays a more important role. Knock-in mouse line, in which the SHP2 signal was disrupted (gp130F759/F759 group), and wild-type mice (WT group) were used. A whole-cell patch clamp experiment was performed, and intracellular Ca2+ concentration ([Ca2+]i transient) was monitored. The ICaL density and [Ca2+]i transient were measured from the untreated cells and the cells treated with LIF or IL-6 and soluble IL-6 receptor (IL-6 + sIL-6r). Action potential duration (APD) was also recorded from the ventricle of each mouse, with or without LIF. Both LIF and IL-6 + sIL-6r increased ICaL density significantly in WT (+ 27.0%, n = 16 p < 0.05, and + 32.2%, n = 15, p < 0.05, respectively), but not in gp130F759/F759 (+ 9.4%, n = 16, NS, and − 6.1%, n = 13, NS, respectively). Administration of LIF and IL-6 + sIL-6r increased [Ca2+]i transient significantly in WT (+ 18.8%, n = 13, p < 0.05, and + 32.0%, n = 21, p < 0.05, respectively), but not in gp130F759/F759 (− 3.8%, n = 7, NS, and − 6.4%, n = 10, NS, respectively). LIF prolonged APD80 significantly in WT (10.5 ± 4.3%, n = 12, p < 0.05), but not in gp130F759/F759 (− 2.1 ± 11.2%, n = 7, NS). SHP2-mediated signaling cascade is essential for the LIF and IL-6 + sIL-6r-dependent increase in ICaL, [Ca2+]i transient and APD.
Journal: Journal of Molecular and Cellular Cardiology - Volume 43, Issue 6, December 2007, Pages 710–716