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Effects of molecular chaperone 4-phenylbutyric acid on cell damage of steatotic HepG2 cells

FAN Zhu-ping, AI Luo-yan, CHEN Li-ping, WU Chang-wei, CHEN Zhi-wei, SU Da-zhi, XU Qing-qing, WANG Xiao-han   

  1. Department of Health Care Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai 200127, China
  • Online:2014-12-28 Published:2014-12-30
  • Supported by:

    Key Discipline Construction Project of Shanghai Public Health,12GWZX0903

Abstract:

Objective To observe the occurrence of endoplasmic reticulum stress in steatotic HepG2 cells and to explore the effects of chemical molecular chaperone 4-phenylbutyric acid (4-PBA) on the endoplasmic reticulum stress, oxidative stress, and apoptosis of steatotic HepG2 cells. Methods HepG2 cells were intervened by fatty acid mixtures of 0.5 mmol/L and 1.0 mmol/L. The mRNA expressions of endoplasmic reticulum stress related protein CHOP and glucose regulated protein 78 (GRP78) were detected by the Real-time PCR at different time points. Then steatotic HepG2 cells were intervened by 4-PBA of 2 mmol/L. At different time points, the mRNA expressions of CHOP and GRP78 and levels of malonaldehyde (MDA), which was the oxidative stress index, superoxide dismutase (SOD), and reduced glutathione (GSH) were detected and variations of the viability of apoptosis related protein Caspase-3 were observed. Results Compared to the control group, the mRNA expressions of CHOP and GRP78 in HepG2 cells of fatty acid intervened group increased significantly (P<0.05). The intervention of 4-PBA decreased the mRNA expressions of CHOP and GRP78 in steatotic HepG2 cells (P<0.05) and MDA level; significantly increased SOD and GSH levels (P<0.05); and decreased the viability of Caspase-3 (P<0.05). Conclusion Significant endoplasmic reticulum stress occurs in steatotic HepG2 cells. Molecular chaperone 4-PBA may alleviate oxidative stress and endoplasmic reticulum stress, decrease the viability of Caspase-3 of steatotic HepG2 cells, and alleviate the cell damage.

Key words: steatotic HepG2 cells, oxidative stress, endoplasmic reticulum stress, Caspase-3, 4-phenylbutyric acid