کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5509212 | 1538508 | 2017 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cobalt chloride induces RhoA/ROCK activation and remodeling effect in H9c2 cardiomyoblasts: Involvement of PI3K/Akt and MAPK pathways
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Chronic heart failure is a serious complication of myocardial infarction, one of the major causes of death worldwide that often leads to adverse cardiac hypertrophy and poor prognosis. Hypoxia-induced cardiac tissue remodeling is considered an important underlying etiology. This study aimed to delineate the signaling profiles of RhoA/ROCK, PI3K/Akt, and MAPK and their involvement in regulation of remodeling events in cultured H9c2 cardiomyoblast cells. In addition to its growth-suppressive effect, the hypoxia-mimetic chemical, cobalt chloride (CoCl2) significantly induced RhoA kinase activation as revealed by increased MBS phosphorylation and ROCK1/2 expression in H9c2 cells. CoCl2 treatment up-regulated type I collagen and MMP-9, but did not affect MMP-2, implicating its role in tissue remodeling. Kinetic signal profiling study showed that CoCl2 also elicited Smad2 hyperphosphorylation and its nuclear translocation in the absence of TGF-β1. In addition, CoCl2 activated Akt-, ERK1/2-, JNK-, and p38 MAPK-mediated signaling pathways. Kinase inhibition experiments demonstrated that hydroxyfasudil, a RhoA kinase inhibitor, significantly blocked the CoCl2- and lysophosphatidic acid-evoked Smad2 phosphorylation and overexpression of type I collagen and MMP-9, and that PI3K and ERK interplayed with RhoA and its downstream Smad2 signaling cascade. In conclusion, this study demonstrated that RhoA/ROCK, PI3K/Akt, and MAPK pathways are mechanistically involved in the CoCl2-stimulated tissue remodeling in H9c2 cardiomyoblast cells. Targeting signaling mediators might be used to mitigate hypoxia-related Smad2 phosphorylation and cardiac remodeling events in ischemic cardiomyopathy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 36, August 2017, Pages 25-33
Journal: Cellular Signalling - Volume 36, August 2017, Pages 25-33
نویسندگان
Cheng-I Cheng, Yueh-Hong Lee, Po-Han Chen, Yu-Chun Lin, Ming-Huei Chou, Ying-Hsien Kao,