17β‐Estradiol promotes the synthesis and the secretion of annexin I in the CCRF‐CEM human cell line

Abstract

AIMS: Annexin I (ANXA1), a 37kDa member of the annexin family of Ca2+-binding and phospholipid-binding proteins, is particularly abundant in various populations of peripheral blood leukocytes. Since this protein modulates the anti-inflammatory actions of the steroid hormones, the purpose of this study was to investigate the effects of the female sex steroid hormone, 17beta-estradiol (E2beta), on the synthesis and secretion of ANXA1 in the human CCRF-CEM acute lymphoblastic leukemia cell line. METHODS: Complementary reverse transcription-polymerase chain reaction and Western blot assays were performed to study the effect of E2beta on the expression of mRNA and protein ANXA1, respectively. RESULTS AND DISCUSSION: Treatment of CCRF-CEM cells with E2beta, for 30 min, stimulated the synthesis of ANXA1 mRNA molecules, and increased the cellular level of ANXA1 protein. Moreover, when the cells were incubated with E2beta under the same experimental conditions, a significant increase in the amount of ANXA1 secreted from the cells was also detected. ICI 182,780, a selective inhibitor of the intracellular estrogen receptor, had no effect on the E2beta-stimulated expression and externalisation of ANXA1. Taken together, these results indicate that E2beta induces de novo synthesis of ANXA1 and stimulates its secretion in the CCRF-CEM cell line, apparently through a mechanism independent of the intracellular estrogen receptor.

Modulatory Effect of Phytoestrogens and Curcumin on Induction of Annexin 1 in Human Peripheral Blood Mononuclear Cells and their Inhibitory Effect on Secretory Phospholipase A₂

“…Moreover, a significant increase in the amount of ANXA1 excreted out of plasma membrane was also observed. It has been reported that the increase in the cellular turnover ofANXA1 may cause a rapid export of the proteins from intracellular stores to extracellular sites and as a consequence the de novo synthesis of proteins may took place to replenish the depleted intracellular levels [16]. Based on these findings, our results indicate that the investigated compounds may have a potential to efficiently stimulate the ANXA1 secretion.…”

Studies on estrogen receptor (ER) α and β responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists

“…Some of the genes, such as annexin-1 and bcl-x, are known as estrogen-regulated genes (Castro-Caldas et al 2001, Stoltzner et al 2001. A few genes, including mitochondrial uncoupling protein 2 and platelet factor 4, which were regulated by E 2 in our study, have been previously described as estrogen insensitive in other tissues (Norris & Bonnar 1994, Luukkaa et al 2001, Stirone et al 2005.…”

Age-dependent Effects of 17β-estradiol on the Dynamics of Estrogen Receptor β (ERβ) Protein–Protein Interactions in the Ventral Hippocampus

“…This event could potentially explain the presence of structural proteins pulled down in our results. Interestingly, E2 can also modulate the expression of members of the annexin family (42,43), further supporting interplay between annexins and estrogen receptors. Taken together, these results suggest that protective aspects of E2 signaling could be mediated through estrogen receptor-ANXA interactions demonstrated here and in other reports (12,44,45), and unique to this study is an age-related change in some of these associations with ER␤.…”