Selenoprotein P-expression, functions, and roles in mammals

Area of Science:

• Biochemistry
• Molecular Biology
• Nutritional Science

Background:

• Selenoprotein P (Sepp1) is a key selenium-carrying protein with distinct N-terminal and C-terminal domains.
• Hepatic synthesis of Sepp1 is crucial for whole-body selenium homeostasis and distribution.
• Sepp1 interacts with lipoprotein receptors like ApoER2 and megalin for selenium uptake and retention in specific organs.

Purpose of the Study:

• To elucidate the diverse functions of Selenoprotein P.
• To investigate the role of Sepp1 domains in selenium distribution and physiological functions.
• To establish plasma Sepp1 concentration as a reliable indicator of selenium nutritional status.

Main Methods:

• Analysis of Sepp1 structure and function, including its domains and selenocysteine residues.
• Investigating Sepp1 interactions with ApoER2 and megalin for organ-specific selenium transport.
• Evaluating the impact of Sepp1 deficiency and domain-specific expression on host defense against *Trypanosoma congolense* infection.
• Correlating plasma Sepp1 levels with selenium nutritional status in experimental models.

Main Results:

• Sepp1 possesses multiple functions, including selenium transport and distribution via interactions with specific receptors.
• The N-terminal domain of Sepp1, containing a redox motif, is responsible for its protective effects against *Trypanosoma congolense* infection.
• Mice lacking Sepp1 exhibit increased susceptibility to infection, while those expressing only the N-terminal domain are protected.
• Plasma Sepp1 concentration decreases during selenium deficiency, highlighting its utility as a nutritional biomarker.

Conclusions:

• Selenoprotein P plays a critical role in selenium homeostasis, organ distribution, and host defense.
• The N-terminal redox domain of Sepp1 is essential for its protective function against parasitic infections.
• Plasma Sepp1 concentration serves as a valuable biomarker for assessing selenium nutritional status.