Chlorogenic acid against palmitic acid in endoplasmic reticulum stress-mediated apoptosis resulting in protective effect of primary rat hepatocytes

Yong Zhang,Jianrui Lv,Liangsheng Miao,Huijuan Zhang,Gang Wu,Zhenni Zhang

doi:10.1186/s12944-018-0916-0

Abstract

BackgroundWe demonstrated growing evidence supports a protective role of chlorogenic acid of rat hepatocytes elicited by two compounds, i.e. thapsigargin and palmitic acid. Nevertheless, little is known about the mechanisms of palmitic acid induced endoplasmic reticulum (ER) stress and cell death.MethodsThe proliferation of primary rat hepatocytes was detected by MTT assay. The expression of GRP78, CHOP and GRP94 was detected by Western blot analyses.Caspase-3 activity was detected by a Caspase-3 substrate kit. Cell apoptosis was detected by Hoechst 33342 staining.ResultsWe demonstrated that incubation of hepatocytes for 16 h with palmitic acid elevated cell death. Moreover, Western blot analyses demonstrated increased levels of the endoplasmic reticulum stress markers — glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and glucose regulated protein 94 (GRP94). Chlorogenic acid could inhibit ER stress induced cell death and levels of indicators of ER stress caused by palmitic acid. The effect of thapsigargin, which evokes ER stress were reversed by chlorogenic acid.ConclusionsAltogether, our data indicate that in primary rat hepatocytes, chlorogenic acid prevents ER stress-mediated apoptosis of palmitic acid.

Highlights

Hepatocyte death is associated with almost every hepatopathy.In recent studies, thapsigargin (TG) has found such widespread use since it pumps Ca2+ from the cytosol into the lumen of the endoplasmic reticulum (ER) in cells [1].During the last thirty years, the mechanism of TG action has been illustrated thoroughly [2]
We report that: (1) palmitic acid could induce ER stress and apoptosis in hepatocytes; (2) chlorogenic acid could reduce cell death induced by palmitic acid; (3) with specific attention given to glucose regulated protein 78 (GRP78), glucose regulated protein 94 (GRP94) and C/EBP homologous protein (CHOP), we can adjust the effects through alteration of the ER stress
Chlorogenic acid inhibited palmitic acid induced cell death Primary rat hepatocytes treated with 250 μmol/l palmitic and 5 μmol/l chlorogenic acid presented restored cell viability to levels observed in untreated cells (Fig. 1)

Summary

Introduction

Hepatocyte death is associated with almost every hepatopathy.In recent studies, thapsigargin (TG) has found such widespread use since it pumps Ca2+ from the cytosol into the lumen of the endoplasmic reticulum (ER) in cells [1].During the last thirty years, the mechanism of TG action has been illustrated thoroughly [2]. Thapsigargin (TG) has found such widespread use since it pumps Ca2+ from the cytosol into the lumen of the endoplasmic reticulum (ER) in cells [1]. As we all know that raising of intracellular free calcium([Ca2+]i) may cause cell death in many cells such as hepatocytes [3]. Saturated fatty acids (FA) including palmitic acid may cause apoptosis and ER stress in rat and human liver cell. The assumption is confirmed by the fact that palmitic acid induced ER stress and apoptosis are founded in mice and rats [9, 10]. We demonstrated growing evidence supports a protective role of chlorogenic acid of rat hepatocytes elicited by two compounds, i.e. thapsigargin and palmitic acid. Little is known about the mechanisms of palmitic acid induced endoplasmic reticulum (ER) stress and cell death

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