The Nuclear Orphan Receptor NR4A1 is Involved in the Apoptotic Pathway Induced by LPS and Simvastatin in RAW 264.7 Macrophages.
- Author:
Yong Chan KIM
1
;
Seok Bean SONG
;
Sang Kyu LEE
;
Sang Min PARK
;
Young Sang KIM
Author Information
- Publication Type:Original Article
- Keywords: NR4A1; Apoptosis; LPS; Simvastatin; Macrophages
- MeSH: Animals; Apoptosis; Arthritis; bcl-2-Associated X Protein; Cell Death; Child; Child, Orphaned*; DNA Fragmentation; Humans; Macrophages*; Membrane Potential, Mitochondrial; Mice; Mitochondria; Pathology; Sepsis; Simvastatin*
- From:Immune Network 2014;14(2):116-122
- CountryRepublic of Korea
- Language:English
- Abstract: Macrophage death plays a role in several physiological and inflammatory pathologies such as sepsis and arthritis. In our previous work, we showed that simvastatin triggers cell death in LPS-activated RAW 264.7 mouse macrophage cells through both caspase-dependent and independent apoptotic pathways. Here, we show that the nuclear orphan receptor NR4A1 is involved in a caspase-independent apoptotic process induced by LPS and simvastatin. Simvastatin-induced NR4A1 expression in RAW 264.7 macrophages and ectopic expression of a dominant-negative mutant form of NR4A1 effectively suppressed both DNA fragmentation and the disruption of mitochondrial membrane potential (MMP) during LPS- and simvastatin-induced apoptosis. Furthermore, apoptosis was accompanied by Bcl-2-associated X protein (Bax) translocation to the mitochondria. Our findings suggest that NR4A1 expression and mitochondrial translocation of Bax are related to simvastatin-induced apoptosis in LPS-activated RAW 264.7 macrophages.
