title: P-cresol induces disruption of cardiomyocyte adherens junctions.
abstract: 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.
authors: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Yu-Sen
authors: YS
authors: Peng
authors: Yen-Tung
authors: YT
authors: Lin
authors: Sheng-De
authors: SD
authors: Wang
authors: Kuan-Yu
authors: KY
authors: Hung
authors: Ying
authors: Y
authors: Chen
authors: Seu-Mei
authors: SM
authors: Wang
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003408:Cresols / Q000633:toxicity*; D005260:Female; D008297:Male; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats
chemical_list: D015820:Cadherins; D002227:Carbazoles; D003408:Cresols; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C081021:Go 6976; C032538:4-cresol; D051571:Protein Kinase C-alpha