Interaction between lanthanide ions and Saccharomyces cerevisiae cells

Area of Science:

• Biochemistry
• Cell Biology
• Toxicology

Background:

• Lanthanides (Ln³⁺) are non-essential elements with significant imaging and therapeutic potential.
• Trivalent lanthanide ions are known Ca²⁺ channel blockers, but correlations between their accumulation, toxicity, and blocking activity are not well-established.
• Understanding these correlations is crucial for safe and effective application of lanthanides.

Purpose of the Study:

• To investigate the relationship between lanthanide ion (Ln³⁺) accumulation, toxicity, and Ca²⁺ channel blocking activity in Saccharomyces cerevisiae.
• To determine how different lanthanide concentrations affect Ca²⁺ influx into yeast cells.
• To identify the role of the Cch1/Mid1 Ca²⁺ channel in lanthanide uptake.

Main Methods:

• Utilized Saccharomyces cerevisiae as a eukaryotic model system.
• Investigated exogenous stress-induced Ca²⁺ influx.
• Measured Ln³⁺ accumulation and Ca²⁺ channel blocking activity at various concentrations.
• Assessed the contribution of the Cch1/Mid1 Ca²⁺ channel to lanthanide entry.

Main Results:

• Ln³⁺ blocked Ca²⁺ entry into yeast cells only at high concentrations, sufficient for rapid cell surface binding.
• At lower concentrations, Ln³⁺ were internalized but did not effectively block Ca²⁺ influx.
• Most Ln³⁺ ions blocked Ca²⁺ entry at 1 mM, with exceptions including La³⁺, Pr³⁺, and Nd³⁺.
• The Cch1/Mid1 Ca²⁺ channel was implicated in the cellular uptake of La³⁺ and Gd³⁺, showing a preference for La³⁺.

Conclusions:

• Lanthanide ion (Ln³⁺) efficacy as Ca²⁺ channel blockers is concentration-dependent, requiring high levels for surface binding and inhibition.
• The Cch1/Mid1 Ca²⁺ channel plays a role in the cellular accumulation of specific lanthanides.
• These findings suggest the potential for developing methods to load cells with controlled amounts and ratios of lanthanides.