Stress-induced activation of GATA-4 in cardiac muscle cells.
Stress-induced activation of GATA-4 in cardiac muscle cells.
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DOI：
10.1016/s0891-5849(03)00208-9
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发表时间：
2003-06
影响因子：
7.4
通讯作者：
Yuichiro J. Suzuki
中科院分区：
文献类型：
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作者：
Yuichiro J. Suzuki
GATA-4 调节心脏中的基因转录。这项研究检验了 GATA-4 是否受到应激诱导的信号事件的影响。用汞处理 HL-1 心肌细胞会诱导细胞凋亡，而细胞凋亡则被过氧化氢酶的过度表达所阻断。与柔红霉素 (DNR) 类似，汞会导致 GATA-4 mRNA 表达下调。然而，与 DNR 相比，汞诱导细胞凋亡的效果较差。 GATA-4 蛋白表达和活性的分析表明，汞最初增强了 GATA-4 DNA 结合活性，随后下调了 GATA-4 表达。汞诱导的 GATA-4 激活与 GATA-4 的磷酸化有关，这似乎是通过 MEK/ERK 途径发生的。与未磷酸化的 GATA-4 相比，汞或放线菌素 D 降低磷酸化 GATA-4 的水平的速度更慢，这表明磷酸化的 GATA-4 更能抵抗细胞降解。与先前的发现一致，即 GATA-4 磷酸化诱导细胞存活，汞减少了 DNR 诱导的细胞死亡。这些结果表明，心肌细胞通过引发 MEK/ERK 信号传导形成磷酸化 GATA-4 来响应汞应激，从而更能抵抗细胞降解并诱导细胞存活。
GATA-4 regulates gene transcription in the heart. This study examined whether GATA-4 is influenced by stress-induced signaling events. Treatment of HL-1 cardiac muscle cells with mercury results in the induction of apoptosis that is blocked by overexpression of catalase. Similar to daunorubicin (DNR), mercury causes downregulation of GATA-4 mRNA expression. However, mercury is less effective in inducing apoptosis compared to DNR. Analyses of GATA-4 protein expression and activity reveal that mercury initially enhances the GATA-4 DNA-binding activity, before subsequent downregulation of GATA-4 expression. The mercury-induced GATA-4 activation is associated with a phosphorylation of GATA-4, which appears to occur via the MEK/ERK pathway. The level of phosphorylated GATA-4 is more slowly decreased by mercury or actinomycin D, compared to unphosphorylated GATA-4, suggesting that phosphorylated GATA-4 is more resistant to cellular degradation. Consistent with a previous finding that GATA-4 phosphorylation induces cell survival, mercury decreases cell death induced by DNR. These results suggest that cardiac muscle cells respond to mercury stress by eliciting MEK/ERK signaling to form phosphorylated GATA-4 that is more resistant to cellular degradation and induce cell survival.