<italic style="font-style: italic">Pollen Typhae</italic> Total Flavone Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway

Ming-tai CHEN; Ruo-lan HUANG; Li-jun OU; Ying-nan CHEN; Ling MEN; Xiao CHANG; Ling WANG; Yu-zhu YANG; Zhong ZHANG

doi:10.1007/s11655-019-3052-4

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Pollen Typhae Total Flavone Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway

Original Article | Updated：2021-08-27

- Pollen Typhae Total Flavone Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway
- Chinese Journal of Integrative Medicine Vol. 25, Issue 8, Pages: 604-612(2019)
- Affiliations：
  
  Cardiovascular Department, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen (518000), China
- Author bio：
  
  Correspondence to: Prof. ZHANG Zhong, Tel: 86-755-88359899, E-mail: szszyyzz@163.com
- Funds：
- DOI：10.1007/s11655-019-3052-4
  CLC：
- Published：01 August 2019，
  
  Published Online：01 February 2019，
  
  Accepted：17 May 2017
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Ming-tai CHEN, Ruo-lan HUANG, Li-jun OU, et al. Pollen Typhae Total Flavone Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway. [J]. Chinese Journal of Integrative Medicine 25(8):604-612(2019)
DOI：

Ming-tai CHEN, Ruo-lan HUANG, Li-jun OU, et al. Pollen Typhae Total Flavone Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway. [J]. Chinese Journal of Integrative Medicine 25(8):604-612(2019) DOI： 10.1007/s11655-019-3052-4.

摘要

Abstract

Objective:

To test the hypothesis that the inhibition of endoplasmic reticulum (ER) stress-induced apoptosis in oxidized low-density lipoproteins (ox-LDL)-induced human aortic-vascular smooth muscle cells (HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein homologous protein (CHOP) signaling pathway by

Pollen Typhae

total flavone (PTF).

Methods:

Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups

including a normal control group

an ox-LDL group (70 μg/mL high ox-LDL)

an HPTF group (70 μg/mL high ox-LDL+500 μg/mL PTF)

an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF)

and a LPTF group (70 μg/mL high ox-LDL+100 μg/mL PTF) in the first part; and a normal control group

an ox-LDL group (70 μg/mL high ox-LDL)

an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF)

a shRNA group (transducted with PERK shRNA lentiviral particles)

a scramble shRNA group (transducted with control shRNA lentiviral particles)

an MPTF+ox-LDL+shRNA group (250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group (70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot

and their mRNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4

5-dimethylthiazol-2-yl)-2

5-diphenyltetrazolium bromide (MTT) assay was applied to test cell viability

and the level of apoptosis was monitored by flow cytometry.

Results:

The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis

which was attenuated in PTF treatment groups and shRNA groups. Moreover

the ox-LDL group had increased protein and mRNA levels of binding immunoglobulin protein and ER-associated apoptosis proteins

such as PERK

eIF2α

ATF4 and CHOP

which were attenuated in PTF treatment groups and shRNA groups.

Conclusions:

The apoptosis induced by ox-LDL had a strong relation to ER stress. The protective effect of PTF on ER stressinduced apoptosis was associated with inhibition of the PERK-eIF2α-ATF4-CHOP pathway

which might be a potential therapeutic strategy for enhancing the stability of atherosclerotic plaques.

关键词

Keywords

Pollen Typhae total flavoneendoplasmic reticulum stressprotein kinase RNA-like endoplasmic reticulum kinase-eukaryotic translation initiation factor 2α-activating transcription factor 4-CCAAT/enhancer binding protein homologous protein pathwayapoptosisvulnerable atherosclerotic plaque

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Pollen Typhae Total Flavone Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis in Human Aortic-Vascular Smooth Muscle Cells through Down-Regulating PERK-eIF2α-ATF4-CHOP Pathway

DOI：10.1007/s11655-019-3052-4

摘要

Abstract

关键词

Keywords

references