A putative lectin-binding receptor mediates cadmium-evoked calcium release

Area of Science:

• Cell Biology
• Toxicology
• Biochemistry

Background:

• Cadmium (Cd2+) exposure triggers intracellular calcium (Ca2+) release in human dermal fibroblasts, primarily through inositol trisphosphate pathways.
• The mechanism by which Cd2+ induces this calcium release is not fully understood.

Purpose of the Study:

• To investigate the role of cell surface glycoproteins in mediating the cellular response to cadmium exposure.
• To identify potential receptors involved in cadmium-induced calcium release.

Main Methods:

• Utilized lectins, specifically wheat germ agglutinin (WGA), to probe for cell surface interactions with cadmium.
• Measured cytosolic free Ca2+ and 45Ca2+ efflux to quantify calcium release.
• Assessed the binding affinity of fluoresceinylated WGA and the effect of chitotriose on WGA binding and cadmium responsiveness.
• Investigated the role of N-acetylneuraminic acid and N-acetylglucosamine by using succinylated WGA.

Main Results:

• Wheat germ agglutinin (WGA) significantly inhibited Cd2+-evoked calcium release in a dose-dependent manner (half-maximal inhibition at 1.2 x 10(-7) M).
• WGA binding to cells was reversible by chitotriose, which also restored cadmium responsiveness.
• WGA's inhibitory effect was mediated by binding to N-acetylneuraminic acid, as succinylated WGA (binding N-acetylglucosamine) did not inhibit calcium release.
• WGA did not directly bind or affect the uptake of cadmium (109Cd2+).

Conclusions:

• A cell surface glycoprotein containing N-acetylneuraminic acid likely acts as a receptor mediating cadmium-induced calcium release in human dermal fibroblasts.
• Wheat germ agglutinin (WGA) binding to this receptor inhibits the cadmium response, providing a novel insight into cadmium toxicity mechanisms.