IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Gαq interaction and protein kinase C-α/CaMKII activation in H9c2 cardiomyoblast cells
IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Gαq interaction and protein kinase C-α/CaMKII activation in H9c2 cardiomyoblast cells
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DOI：
10.1677/joe-07-0619
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发表时间：
2008-05-01
影响因子：
4
通讯作者：
Huang, Chih-Yang
中科院分区：
文献类型：
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作者：
Chu, Chun-Hsien;Tzang, Bor-Show;Huang, Chih-Yang
人们对 IGF-II 通过心脏组织中 IGF-II/6-磷酸甘露糖受体 (IGF2R) 的信号转导所发挥的作用知之甚少。在我们之前的研究中，我们检测到病理性肥大的心肌细胞中 IGF-II 和 IGF2K 的表达增加。我们假设与 IGF-II 结合后，IGF2K 可能触发细胞内信号级联反应，参与病理性心脏肥大的进展。在本研究中，我们利用人体心血管组织芯片的免疫组织化学分析来检测IGF2K的表达。在我们对 H9c2 心肌细胞培养物的研究中，我们使用罗丹明鬼笔环肽染色来测量细胞肥大，并使用蛋白质印迹来测量用 IGF-II 处理的细胞中心脏肥大市场心房钠尿肽 (ANP) 和脑钠尿肽 (BNP) 的表达。我们发现 IMP 过度表达与心肌梗死之间存在显着关联。 IGF-II处理H9c2心肌细胞不仅诱导细胞肥大，而且增加ANP和BNP的蛋白水平。使用 Leu27IGF-II（IGF-II 的类似物，选择性地与 IGF2R 相互作用，特异性激活 IGF2R 信号级联反应），我们发现 Leu271GF-II 与 IGF2R 的结合，导致蛋白激酶 C (PKC)-α 和钙/钙调蛋白依赖性蛋白激酶 II (CaMKII) 以 G α q 依赖性方式磷酸化全部增加。通过抑制PKC-α/CaMKII活性，我们发现IGF-II和Leu271GF-II诱导的细胞肥大以及ANP和BNP的上调被显着抑制。总而言之，这项研究为 IGF2R 及其下游信号传导在心脏肥大中的作用提供了新的见解。抑制 IGF2R 信号通路可能是预防病理性肥大进展的良好策略。
The role played by IGF-II in signal transduction through the IGF-II/mannose-6-phosphate receptor (IGF2R) in heart tissue has been poorly understood. In our previous studies, we detected an increased expression of IGF-II and IGF2K in cardiomyocytes that had undergone pathological hypertrophy. We hypothesized that after binding with IGF-II, IGF2K may trigger intracellular signaling cascades involved in the progression of pathologically cardiac hypertrophy. In this study, we used immunohistochemical analysis of the human cardiovascular tissue array to detect expression of IGF2K. In Our study of H9c2 cardiomyoblast cell cultures, we used the rhodamine phalloidin staining, to measure the cell hypertrophy and western blot to measure the expression of cardiac hypertrophy markets atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cells treated with IGF-II. We found that a significant association between IMP, overexpression and myocardial infarction. The treatment of H9c2 cardiomyoblast cells with IGF-II not only induced cell hypertrophy but also increased the protein level of ANP and BNP. Using Leu27IGF-II, an analog of IGF-II which interacts selectively with the IGF2R to specifically activate IGF2R signaling cascades, we found that binding of Leu271GF-II to IGF2R), led to all increase in the phosphorylation of protein Kinase C (PKC)-alpha and calcium/calmodulin-dependent protein kinase II (CaMKII) in a G alpha q-dependent manner. By the inhibition of PKC-alpha/CaMKII activity, we found that IGF-II and Leu271GF-II-induced cell hypertrophy and upregulation of ANP and BNP were significantly suppressed. Taken together, this study provides a new insight into the effects of the IGF2R and its downstream signaling in cardiac hypertrophy. The suppression of IGF2R signaling pathways may be a good strategy to prevent the progression of pathological hypertrophy.