Sialyltransferase7A, a Klf4-responsive gene, promotes cardiomyocyte apoptosis during myocardial infarction

Abstract

Myocardial infarction (MI) is one major cause of heart failure through its induction of cardiomyocyte death. However, the molecular mechanisms associated with MI-induced cardiomyocyte apoptosis in the context of sialylation of heart are not yet understood. In this study, we found that sialyltransferase7A (Siat7A), one of the members of sialyltransferase family, was significantly increased in the ischemic myocardium, as well as in the human cardiomyocyte cell line AC16 under hypoxic condition. The Sialyl-Tn antigen (Neu5Acα2-6GalNAc-O-Ser/Thr) synthesized by Siat7A also increased in the AC16 cardiomyocytes following hypoxic stimulus. Increased Siat7A promoted cardiomyocyte apoptosis. The knockdown of Siat7A expression reduced cardiomyocyte apoptosis in both of vivo and vitro. Furthermore, the decreased extracellular signal-regulated kinase ERK1 and ERK2 (ERK1/2) activity was involved in the Siat7A-induced cardiomyocyte apoptosis. Notably, we showed that Krüppel-like factor 4 (Klf4), one of the transcription factors, specifically bound to the Siat7A promoter by ChIP assays. Deletion and mutagenesis analysis identified that Klf4 could transactivate the Siat7A promoter region (nt -655 to -636 bp). The upregulated Siat7A expression, which was paralleled by the increased Klf4 in the ischemic myocardium, contributed to cardiomyocyte apoptosis. Our study suggests Siat7A could be a valuable target for developing treatments for MI patients.

Analysis of region specific gene expression patterns in the heart and systemic responses after experimental myocardial ischemia

“…Despite the fact that Klf4 has been implicated in apoptosis, data on Klf4 in ischemic disease are scarce. Our findings are contradictory to a recent publication by Zhang and coworkers [ 51 ] who showed an increased expression of Klf4 in injured cardiomyocytes following MI. However, in this study the authors did not distinguish between cytoplasmic and nuclear expression of Klf4 and the experiments were performed in mice.…”

High expression of B23 is associated with tumorigenesis and poor prognosis in bladder urothelial carcinoma

“…Previous studies have reported that B23 is a positive regulator of the ERK signaling pathway and may promote cell proliferation via ERK activity in prostate cancer (14–16). Therefore, to investigate whether B23 affected bladder cancer cell growth via the ERK signaling pathway, the present study detected the protein expression levels of p-ERK, and it was observed that the phosphorylation of ERK was inhibited by B23 knockdown; however, the total protein expression levels of ERK remained unaltered (Fig.…”

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