Role of selenoprotein P expression in the function of pancreatic ß cells: Prevention of ferroptosis-like cell death and stress-induced nascent granule degradation.
Free Radic Biol Med
; 183: 89-103, 2022 04.
Article
en En
| MEDLINE
| ID: mdl-35318102
ABSTRACT
Selenoprotein P (SELENOP) is a major selenium (Se)-containing protein (selenoprotein) in human plasma that is mainly synthesized in the liver. SELENOP transports Se to the cells, while SELENOP synthesized in peripheral tissues is incorporated in a paracrine/autocrine manner to maintain the levels of cellular selenoproteins, called the SELENOP cycle. Pancreatic ß cells, responsible for the synthesis and secretion of insulin, are known to express SELENOP. Here, using MIN6 cells as a mouse model for pancreatic ß cells and Selenop small interfering (si)RNA, we found that Selenop gene knockdown (KD) resulted in decreased cell viability, cellular pro/insulin levels, insulin secretion, and levels of several cellular selenoproteins, including glutathione peroxidase 4 (Gpx4) and selenoprotein K (Selenok). These dysfunctions induced by Selenop siRNA were recovered by the addition of Se. Ferroptosis-like cell death, regulated by Gpx4, was involved in the decrease of cell viability by Selenop KD, while stress-induced nascent granule degradation (SINGD), regulated by Selenok, was responsible for the decrease in proinsulin. SINGD was also observed in the pancreatic ß cells of Selenop knockout mice. These findings indicate a significant role of SELENOP expression for the function of pancreatic ß cells by maintaining the levels of cellular selenoproteins such as GPX4 and SELENOK.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Selenio
/
Células Secretoras de Insulina
/
Selenoproteína P
/
Ferroptosis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2022
Tipo del documento:
Article