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Resveratrol, an activator of SIRT1, improves ER stress by increasing clusterin expression in HepG2 cells

  • Jinmi Lee
  • Seok-Woo Hong
  • Hyemi Kwon
  • Se Eun Park
  • Eun-Jung Rhee
  • Cheol-Young Park
  • Ki-Won Oh
  • Sung-Woo Park
  • Won-Young LeeEmail author
Original Paper
  • 67 Downloads

Abstract

Endoplasmic reticulum stress (ER stress) is involved in lipid metabolism and lipotoxicity and can lead to apoptosis. Resveratrol, a sirtuin 1 (SIRT1) agonist, prevents ER stress and improves ER stress-induced hepatic steatosis and cell death. Clusterin is a secreted chaperone and has roles in various physiological processes. However, changes in the expression of clusterin upon ER stress and the connection between SIRT1 and clusterin in protection against ER stress are not well known. In cells treated with tunicamycin, resveratrol increased the expression of clusterin mRNA and protein and the secreted clusterin protein level in conditioned medium. Resveratrol decreased protein expression of the ER stress markers, p-PERK, p-IRE1α, and CHOP, and increased the expression of the ER-associated degradation (ERAD) factors, SEL1L and HRD1, in tunicamycin-treated cells. However, no changes in the expression of these genes were observed in clusterin siRNA-transfected cells. Moreover, increased LAMP2 and LC3 expression and decreased Rubicon expression were observed in cells treated with resveratrol or secreted clusterin. These data suggest that SIRT1 activation by resveratrol attenuates ER stress by promoting protective processes such as ERAD and autophagy pathways and that these protective effects are mediated by clusterin.

Keywords

Clusterin ER stress SIRT1 Chaperone Autophagy ERAD 

Abbreviations

CHOP

C/EBP homologous protein

ER

Endoplasmic reticulum

NAFLD

Non-alcoholic fatty liver disease

ERAD

ER-associated degradation

HSP

Heat shock protein

IRE1α

Inositol-requiring enzyme 1α

PERK

Protein kinase RNA-like endoplasmic reticulum kinase

SERCA2b

Sarco(endo)plasmic reticulum Ca2+-ATPase 2b

sCLU

Secretory clusterin

SIRT1

Silent mating-type information regulation 2 homolog 1

UPR

Unfolded protein response

Notes

Funding information

This study was supported by the Medical Research Funds from Kangbuk Samsung Hospital, and the National Research Foundation (NRF), which is funded by the Korean government (NRF-2018R1D1A1B07049689) (http://www.nrf.re.kr). The funders had no role in the study design, data collection, and analysis, the decision to publish, or preparation of the manuscript.

Supplementary material

12192_2019_1012_MOESM1_ESM.pdf (132 kb)
ESM 1 (PDF 132 kb)

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Copyright information

© Cell Stress Society International 2019

Authors and Affiliations

  • Jinmi Lee
    • 1
  • Seok-Woo Hong
    • 1
  • Hyemi Kwon
    • 2
  • Se Eun Park
    • 2
  • Eun-Jung Rhee
    • 2
  • Cheol-Young Park
    • 2
  • Ki-Won Oh
    • 2
  • Sung-Woo Park
    • 2
  • Won-Young Lee
    • 2
    Email author
  1. 1.Institute of Medical Research, Kangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoulRepublic of Korea
  2. 2.Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoulRepublic of Korea

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