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KMID : 1149220180260040307
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Korean Journal of Oriental Medical Prescription
2018 Volume.26 No. 4 p.307 ~ p.318
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Inhibitory Effects of Litsea japonica Flesh Water Extract against Endoplasmic Reticulum Stress in HepG2 Cells
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Kim Eun-Ok
Jegal Kyung-Hwan
Kim Jae-Kwang
Lee Ju-Sang
Park Chung-A
Kim Sang-Chan
Cho Il-Je
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Abstract
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Objectives: Endoplasmic reticulum (ER) stress designates cellular responses to the accumulation of misfolded and unfolded proteins in ER, which is related to a variety of liver diseases. Present study investigated the inhibitory effects of Litsea japonica flesh water extract (LJE) aganist ER stress.
Methods: After HepG2 cells were pretreated with LJE and subsequently exposed to tunicamycin (Tm) or thapsigargin (Tg), expression of C/EBP homologous protein (CHOP), glucose regulated protein 78 kDa (GRP78), asparagine synthetase (ASNS), and endoplasmic reticulum DnaJ homologue 4 (ERDJ4) were determined by immunoblot and real-time PCR analysis. Three canonical signaling pathways in response to ER stress were examined to explore molecular mechanisms involved.
Results: Pretreatment of 1 mg/mL LJE inhibited Tm- or Tg-induced CHOP expression, while L. japonica fruit water extract did not. In addition, LJE decreased the levels of GRP78, ASNS, and ERDJ4 mRNA by Tm. Moreover, phosphorylations of eukaryotic translation initiation factor 2α and inositol-requiring enzyme 1, expression of nuclear form of activating transcription factor 6α, and transactivation of ER stress response element- and unfolded protein response element-harboring luciferase activities were inhibited by LJE pretreatment.
Conclusions: Present results suggest that LJE would be a candidate to prevent or treat ER stress-mediated liver injuries.
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KEYWORD
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Endoplsmic reticulum (ER) stress, HepG2 cells, Litsea japonica flesh water extract (LJE), Tunicamycin (Tm), Unfolded protein response (UPR)
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