Stress-induced activation of GATA-4 in cardiac muscle cells.
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.
Suzuki
Yuichiro J
YJ
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. yuichiro.suzuki@tufts.edu
D000256:Adenoviridae; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D050991:GATA4 Transcription Factor; D008628:Mercury / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D016335:Zinc Fingers
D000903:Antibiotics, Antineoplastic; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D011500:Protein Synthesis Inhibitors; D014157:Transcription Factors; D003609:Dactinomycin; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; D008628:Mercury; D003630:Daunorubicin