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The Nuclear Orphan Receptor NR4A1 is Involved in the Apoptotic Pathway Induced by LPS and Simvastatin in RAW 264.7 Macrophages

  • Kim, Yong Chan (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
  • Song, Seok Bean (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
  • Lee, Sang Kyu (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
  • Park, Sang Min (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
  • Kim, Young Sang (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
  • Received : 2014.01.05
  • Accepted : 2014.03.28
  • Published : 2014.04.30
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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.

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References

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