The interaction of estrogen receptor α and caveolin-3 regulates connexin43 phosphorylation in metabolic inhibition-treated rat cardiomyocytes
| Autor: | Jyun Yan Liang, Tun Hui Chung, Jiahn Chun Wu, Shih-Hung Yang, Seu-Mei Wang |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Aging
medicine.medical_specialty Membrane estrogen receptor Caveolin 3 Fluorescent Antibody Technique Estrogen receptor Biology Biochemistry Receptor tyrosine kinase Estrogen-related receptor alpha chemistry.chemical_compound Membrane Microdomains Internal medicine Centrifugation Density Gradient medicine Animals Myocytes Cardiac Phosphorylation Phosphotyrosine Estrogen receptor beta Microscopy Confocal Estradiol beta-Cyclodextrins Estrogen Receptor alpha Gap Junctions Tyrosine phosphorylation Cell Biology Rats Cell biology Enzyme Activation Pyrimidines src-Family Kinases Endocrinology chemistry Connexin 43 biology.protein Estrogen-related receptor gamma Estrogen receptor alpha hormones hormone substitutes and hormone antagonists Protein Binding Subcellular Fractions |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 41:2323-2333 |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/j.biocel.2009.06.001 |
| Popis: | Caveolin-3, the major caveolin isoform in cardiomyocytes, plays an important role in the rapid signaling pathways initiated by stimulation of the membrane-associated molecules. To examine the role of caveolin-3 in regulating estrogen receptor alpha in cardiomyocytes, we investigate whether the membrane estrogen receptor alpha associates with caveolin-3 and whether this association is linked to the 17beta-estradiol-mediated signals. In control cardiomyocytes, following discontinuous sucrose gradient centrifugation, caveolin-3 was found predominantly in the lipid raft buoyant fractions, whereas it was distributed to both the buoyant and non-lipid raft heavy fractions following metabolic inhibition treatment. Confocal microscopy showed that estrogen receptor alpha co-localized with caveolin-3 on the plasma membrane of neonatal and adult rat cardiomyocytes. This membrane labeling of estrogen receptor alpha was not seen following treatment with the cholesterol-depleting agent methyl-beta-cyclodextrin (5mM), whereas metabolic inhibition had little effect on the membrane distribution of estrogen receptor alpha. Metabolic inhibition induced tyrosine phosphorylation of caveolin-3 and decreased its association with estrogen receptor alpha, both effects being mediated via a Src activation mechanism, since they were inhibited by the selective tyrosine kinase inhibitor PP2. Metabolic inhibition also induced tyrosine phosphorylation of connexin43 and increased its association with c-Src, both effects being prevented by 17beta-estradiol (200 nM). The effect of 17beta-estradiol on metabolic inhibition-induced tyrosine phosphorylation of connexin43 was inhibited by the specific estrogen receptor antagonist ICI182780. These data identify cardiac caveolin-3 as juxtamembrane scaffolding for estrogen receptor alpha docking at caveolae, which provide a unique compartment for conveying 17beta-estradiol-elicited, rapid signaling to regulate connexin43 phosphorylation during ischemia. |
| Databáze: | OpenAIRE |
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