کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5859548 1132482 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Uremic toxin p-cresol induces disassembly of gap junctions of cardiomyocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Uremic toxin p-cresol induces disassembly of gap junctions of cardiomyocytes
چکیده انگلیسی
High serum levels of p-cresol have been associated with cardiovascular diseases. This study investigated the effects of p-cresol on gap junctions in neonatal cultured cardiomyocytes. p-Cresol reduced the spontaneous contraction rates of cardiomyocytes, and caused irregular cardiomyocyte beating. Junctional connexin 43 (Cx43) plaques became smaller in size and the gap junction intercellular communication (GJIC) impaired. Moreover, p-cresol increased intracellular Ca+2 levels, and induced Ca+2-dependent protein kinase Cα (PKCα) activation. p-Cresol decreased P1 and P2 Cx43 levels, and increased non-phosphorylated S368-Cx43 levels. The above changes as well as Cx43 disassembly and GJIC decrease induced by p-cresol were prevented by the BAPTA-AM or PKCα inhibitor Gö6976. These results suggest that PKCα mediates p-cresol-induced gap junction disassembly and GJIC dysfunction via S368-Cx43 serine dephosphorylation. This hypothesis was further confirmed in H9c2 cells by siRNA approach. SiRNA knockdown of PKCα prevented p-cresol-induced increase in nonphosphorylated Cx43. This finding supports the association of p-cresol and cardiovascular diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 302, Issue 1, 8 December 2012, Pages 11-17
نویسندگان
, , , , , ,