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Role of selenoprotein P expression in the function of pancreatic β cells: Prevention of ferroptosis-like cell death and stress-induced nascent granule degradation.
- Source :
-
Free Radical Biology & Medicine . Apr2022, Vol. 183, p89-103. 15p. - Publication Year :
- 2022
-
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 β cells, responsible for the synthesis and secretion of insulin, are known to express SELENOP. Here, using MIN6 cells as a mouse model for pancreatic β 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 β cells of Selenop knockout mice. These findings indicate a significant role of SELENOP expression for the function of pancreatic β cells by maintaining the levels of cellular selenoproteins such as GPX4 and SELENOK. [Display omitted] ● Significant role of SELENOP expression for the function of pancreatic beta cells by maintaining the levels of cellular selenoproteins ● Ferroptosis-like cell death, regulated by Gpx4, was involved in the decrease of cell viability by Selenop KD ● Stress-induced nascent granule degradation, regulated by Selenok, was responsible for the decrease in proinsulin by Selenop KD [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08915849
- Volume :
- 183
- Database :
- Academic Search Index
- Journal :
- Free Radical Biology & Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 156078392
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2022.03.009