Selenium: inhibition of microtubule formation and interaction with tubulin

Area of Science:

• Biochemistry
• Cell Biology
• Toxicology

Background:

• Microtubule proteins (MTP) and tubulin are essential for cellular structure and function.
• Selenium compounds, such as sodium selenite (Na2SeO3), can exhibit biological activity and toxicity.
• Understanding the molecular interactions of selenium with cellular components is crucial for assessing its physiological effects.

Purpose of the Study:

• To investigate the interaction between sodium selenite and microtubule proteins, specifically tubulin.
• To elucidate the mechanism by which sodium selenite affects microtubule polymerization.
• To assess the implications of these interactions in the context of selenium toxicity.

Main Methods:

• Studied the effect of Na2SeO3 on microtubule protein (MTP) and tubulin polymerization in vitro.
• Assessed the binding of known tubulin inhibitors (colchicine and vinblastine) in the presence of selenium.
• Analyzed the formation of disulfide bridges and conformational changes in tubulin.

Main Results:

• Na2SeO3 significantly inhibited MTP polymerization, with half-maximal inhibition at 10 microM.
• Tubulin polymerization was also inhibited by Na2SeO3, though to a lesser extent.
• Evidence suggests selenite induces disulfide bridges between tubulin sulfhydryl groups, causing conformational changes.
• Modified binding of colchicine and vinblastine indicated altered tubulin conformation.

Conclusions:

• Sodium selenite interferes with microtubule dynamics by inhibiting polymerization.
• The mechanism involves the formation of disulfide bonds in tubulin, leading to conformational changes.
• Observed inhibitory concentrations align with known toxic blood levels of selenium, suggesting a potential mechanism for selenium-induced toxicity.