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Effects of CK2 inhibition in cultured fibroblasts from Type 1 Diabetic patients with or without nephropathy

机译:CK2抑制对1型糖尿病肾病或非肾病患者成纤维细胞的影响

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摘要

CK2 is a multifunctional, pleiotropic protein kinase involved in the regulation of cell proliferation and survival. Since fibroblasts from Type 1 Diabetes patients (T1DM) with Nephropathy exhibit increased proliferation, we studied cell viability, basal CK2 expression and activity, and response to specific CK2 inhibitors TBB (4,5,6,7-tetrabenzotriazole) and CX4945, in fibroblasts from T1DM patients either with (T1DM+) or without (T1DM-) Nephropathy, and from healthy controls (N). We tested expression and phosphorylation of CK2-specific molecular targets. In untreated fibroblasts from T1DM+, the cell viability was higher than in both N and T1DM-. CK2 inhibitors significantly reduced cell viability in all groups, but more promptly and with a larger effect in T1DM+. Differences in CK2-dependent phosphorylation sites were detected. In conclusion, our results unveil a higher dependence of T1DM+ cells on CK2 for their survival, despite a similar expression and a lower activity of this kinase compared with those of normal cells.
机译:CK2是一种多功能,多效性蛋白激酶,参与细胞增殖和存活的调节。由于患有肾病的1型糖尿病患者(T1DM)的成纤维细胞显示增生,因此我们在成纤维细胞中研究了细胞活力,基础CK2表达和活性以及对特定CK2抑制剂TBB(4,5,6,7-四苯并三唑)和CX4945的反应来自患有(T1DM +)或没有(T1DM-)肾病的T1DM患者,以及健康对照(N)。我们测试了CK2特异性分子靶标的表达和磷酸化。在未经处理的T1DM +成纤维细胞中,细胞活力均高于N和T1DM-。 CK2抑制剂在所有组中均显着降低了细胞活力,但更迅速且在T1DM +中作用更大。检测到CK2依赖性磷酸化位点的差异。总之,我们的结果揭示了T1DM +细胞对CK2生存的更高依赖性,尽管与正常细胞相比,该激酶的表达相似且活性较低。

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