The Role of Nuclear Factor-E2-Related Factor 1 in the Oxidative Stress Response in MC3T3-E1 Osteoblastic Cells.
BACKGROUND
Reactive oxygen species (ROS) and antioxidants are associated with maintenance of cellular function and metabolism. Nuclear factor-E2-related factor 1 (NFE2L1, Nrf1) is known to regulate the expression of a number of genes involved in oxidative stress and inflammation. The purpose of this study was to examine the effects of NFE2L1 on the response to oxidative stress in osteoblastic MC3T3-E1 cells.


METHODS
The murine calvaria-derived MC3T3-E1 cell line was exposed to lipopolysaccharide (LPS) for oxidative stress induction. NFE2L1 effects were evaluated using small interfering RNA (siRNA) for NFE2L1 mRNA. ROS generation and the levels of known antioxidant enzyme genes were assayed.


RESULTS
NFE2L1 expression was significantly increased 2.4-fold compared to the control group at 10 μg/mL LPS in MC3T3-E1 cells (P<0.05). LPS increased formation of intracellular ROS in MC3T3-E1 cells. NFE2L1 knockdown led to an additional increase of ROS (20%) in the group transfected with NFE2L1 siRNA compared with the control group under LPS stimulation (P<0.05). RNA interference of NFE2L1 suppressed the expression of antioxidant genes including metallothionein 2, glutamatecysteine ligase catalytic subunit, and glutathione peroxidase 1 in LPS-treated MC3T3-E1 cells.


CONCLUSIONS
Our results suggest that NFE2L1 may have a distinct role in the regulation of antioxidant enzymes under inflammation-induced oxidative stress in MC3T3-E1 osteoblastic cells.
Department of Internal Medicine, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea.
So Young
http://orcid.org/0000-0001-6002-0116
SY
Park
Department of Internal Medicine, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea.
Sung Hoon
SH
Kim
Department of Internal Medicine, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea.
Hyun Koo
HK
Yoon
Department of Internal Medicine, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea.
Chang Hoon
CH
Yim
Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. lsk@yumc.yonsei.ac.kr.
Sung Kil
SK
Lim
NF-E2-related factor 1; Osteoblasts; Oxidative stress