EGF stimulates Mg{sup 2+} influx in mammary epithelial cells

Journal Article · Fri Nov 28 04:00:00 EST 2014 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2014.10.125· OSTI ID:22416847

Trapani, Valentina; Arduini, Daniela; Luongo, Francesca

Highlights: • EGF stimulation potentiates Mg{sup 2+} influx into epithelial cells. • EGF-induced Mg{sup 2+} influx does not depend on the concomitantly induced Ca{sup 2+} signal. • EGF-induced Ca{sup 2+} signal is dependent on the presence of extracellular Mg{sup 2+}. • New players in EGF-mediated signaling might be exploited as therapeutic targets. - Abstract: Magnesium is well established as a fundamental factor that regulates cell proliferation. However, the molecular mechanisms linking mitogenic signals, extracellular magnesium availability and intracellular effectors are still largely unknown. In the present study we sought to determine whether EGF regulates magnesium homeostasis in normal HC11 mammary epithelial cells. To this end, we measured Mg{sup 2+} and Ca{sup 2+} fluxes by confocal imaging in live cells loaded with specific fluorescent ion indicators (Mag-Fluo-4 and Fluo-4, respectively). EGF stimulation induces a rapid and sustained increase in intracellular Mg{sup 2+}, concomitantly with a rise in intracellular calcium. The increase in intracellular Mg{sup 2+} derives from an influx from the extracellular compartment, and does not depend on Ca{sup 2+}. On the contrary, the increase in intracellular Ca{sup 2+} derives from intracellular stores, and is impaired in the absence of extracellular magnesium. Inhibition of the EGF receptor tyrosine kinase by Tyrphostin AG1478 markedly inhibits EGF-induced Mg{sup 2+} and Ca{sup 2+} signals. These findings demonstrate that not only does Mg{sup 2+} influx represent an important step in the physiological response of epithelial cells to EGF, but unexpectedly the EGF-induced Mg{sup 2+} influx is essential for the Ca{sup 2+} signal to occur.

• OSTI ID: 22416847
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 454; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CALCIUM
CALCIUM IONS
CATTLE
CELL PROLIFERATION
ETHANE
FLUORESCENCE
GROWTH FACTORS
HOMEOSTASIS
INDICATORS
INHIBITION
MAGNESIUM
RECEPTORS
SOLUTES
STIMULATION
TRANSIENTS
TYROSINE