High concentraction of taurocholic acid induced apoptosis in HTR-8/SVneo cells via overexpression of ERp29 and activation of p38.
BACKGROUND
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disease associated with a significant risk of fetal complications. Our previous study using an iTRAQ-based proteomics approach showed that ERp29 was overexpressed in the placenta tissue of ICP patients, which was an apoptosis-related protein and has not been investigated in the pathogenesis of ICP. The aim of this study was to explore the role of ERp29 in the mechanism of apoptosis in the placenta of ICP.


METHODS
HTR-8/SVneo cells were cultured and treated with different concentrations of taurocholic acid (TCA) (0, 10, 50 and 100 μM). The apoptotic index and cell cycle were detected by flow cytometry; furthermore, the expression levels of ERp29 and p-p38 were detected by western blot. The ERp29-siRNA was also used to confirm the role of ERp29 in TCA induced-apoptosis.


RESULTS
ERp29 expression and the apoptotic index were significantly increased in HTR-8/SVneo cells exposed to 100 μM TCA; so were p-p38 and caspase-3 activity, compared with the 50 μM, 10 μM TCA groups and negative control group (P < 0.05, respectively). The induction of apoptosis by TCA and the expression of p-p38 were reduced in HTR-8/SVneo cells after treatment with ERp29-siRNA, compared with controls (P < 0.05, respectively).


CONCLUSIONS
This study suggested that overexpression of ERp29 may play a key role in TCA-induced apoptosis in HTR-8/SVneo cells via activation of p38, which may participate in the pathogenesis of ICP and may represent a novel target for ICP treatment.
Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China. Electronic address: zhangting040715@163.com.
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Zhang
State Key Laboratory of Reproductive Medicine, Nanjing Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China.
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Zhao
Department of Respiratory Medicine, Jinling Hospital, Nanjing University Medical School, Nanjing 210093, China; Wuxi Second Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
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Luo
Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
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Xiang
Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
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Cheng
Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
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Wang
Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China. Electronic address: chendaozhen@163.com.
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Chen
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D002780:Cholestasis, Intrahepatic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D013656:Taurocholic Acid / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C491738:ERP29 protein, human; D006360:Heat-Shock Proteins; D034741:RNA, Small Interfering; D013656:Taurocholic Acid; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3
Apoptosis; ERp29; Intrahepatic cholestasis of pregnancy; Taurocholic acid