کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5859376 1562350 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
p-Cresol induces disruption of cardiomyocyte adherens junctions
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
p-Cresol induces disruption of cardiomyocyte adherens junctions
چکیده انگلیسی
Higher serum levels of p-cresol in chronic kidney disease populations have been associated with increased cardiovascular mortality. However, studies on how p-cresol affects intercellular junctions between cardiomyocytes were limited. This study investigated the effect of p-cresol on adherens junction (AJ) of neonatal cultured cardiomyocytes and its underlying mechanism. A loss of N-cadherin and p120-catenin (p120ctn) immunostaining from cell-cell contact sites was noted by p-cresol treatment. In addition, p-cresol disrupted AJs by inducing formation of intercellular gaps. Our previous study has revealed that p-cresol increased intracellular calcium levels and activated protein kinase Cα (PKCα) by phosphorylation. The PKCα activation was involved in the p-cresol-mediated AJ disassembly, since pharmacological inhibition of PKCα abolished the above-mentioned p-cresol effect. This PKCα activation also led to the serine dephosphorylation of p120ctn and caused the dissociation of p120ctn from N-cadherin. This hypothesis was further confirmed in H9c2 cells by siRNA approach. SiRNA knockdown of PKCα prevented p-cresol-induced serine dephosphorylation of p120ctn and splitting of AJ. In conclusion, p-cresol caused PKCα-dependent AJ disassembly of cardiomyocytes, which might be related to asychronized contraction.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 306, 5 April 2013, Pages 176-184
نویسندگان
, , , , , ,