Endoplasmic reticulum stress and oxidative stress drive endothelial dysfunction induced by high selenium

Area of Science:

• Biochemistry
• Cell Biology
• Toxicology

Background:

• Selenium is an essential trace element with vital health roles.
• Balanced selenium intake is critical; excessive amounts may pose health risks, including diabetes and endothelial dysfunction.
• Endoplasmic reticulum (ER) stress is implicated in endothelial dysfunction and high selenium toxicity in cancer cells.

Purpose of the Study:

• To investigate the effects of increasing selenite concentrations on endothelial cells.
• To determine if ER stress mediates selenium-induced endothelial dysfunction.
• To explore the role of reactive oxygen species (ROS) in selenium toxicity.

Main Methods:

• Cultured endothelial cells were exposed to varying selenite concentrations.
• Measurements included nitric oxide bioavailability, angiogenesis, ER stress markers, ROS production, and apoptosis.
• Chemical chaperone 4-phenylbutyrate was used to assess the role of ER stress.

Main Results:

• High selenite reduced nitric oxide bioavailability and impaired angiogenesis.
• Elevated selenite induced ER stress, increased ROS production, and promoted apoptosis in endothelial cells.
• 4-phenylbutyrate pretreatment protected cells from selenite-induced toxicity.

Conclusions:

• High selenite exposure leads to endothelial dysfunction via ER stress and ROS production.
• These findings underscore the importance of appropriate selenium supplementation levels.
• Prophylactic selenium supplementation as an antioxidant may carry risks.