The Nuclear Orphan Receptor NR4A1 is Involved in the Apoptotic Pathway Induced by LPS and Simvastatin in RAW 264.7 Macrophages
Immune Network
;
: 116-122, 2014.
Article
in English
| WPRIM
| ID: wpr-121970
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Arthritis
/
Cell Death
/
Apoptosis
/
Sepsis
/
Simvastatin
/
Bcl-2-Associated X Protein
/
DNA Fragmentation
/
Membrane Potential, Mitochondrial
/
Child, Orphaned
Limits:
Animals
/
Humans
Language:
English
Journal:
Immune Network
Year:
2014
Type:
Article
Similar
MEDLINE
...
LILACS
LIS