Calcitriol inhibits HCV infection via blockade of activation of PPAR and interference with endoplasmic reticulum-associated degradation

Yu Min Lin, Hung Yu Sun, Wen Tai Chiu, Hui Chen Su, Yu Chieh Chien, Lee Won Chong, Hung Chuen Chang, Chyi Huey Bai, Kung Chia Young, Chiung Wen Tsao

研究成果: 雜誌貢獻文章

3 引文 (Scopus)

摘要

Vitamin D has been identified as an innate anti-hepatitis C virus (HCV) agent but the possible mechanisms for this issue remain unclear. Here, we clarified the mechanisms of calcitriol-mediated inhibition of HCV infection. Calcitriol partially inhibited HCV infection, nitric oxide (NO) release and lipid accumulation in Huh7.5 human hepatoma cells via the activation of vitamin D receptor (VDR). When cells were pretreated with the activators of peroxisome proliferator-activated receptor (PPAR)-α (Wy14643) and -γ (Ly171883), the calcitriol-mediated HCV suppression was reversed. Otherwise, three individual stimulators of PPAR-α/β/γ blocked the activation of VDR. PPAR-β (linoleic acid) reversed the inhibition of NO release, whereas PPAR-γ (Ly171883) reversed the inhibitions of NO release and lipid accumulation in the presence of calcitriol. The calcitriol-mediated viral suppression, inhibition of NO release and activation of VDR were partially blocked by an inhibitor of endoplasmic reticulum-associated degradation (ERAD), kifunensine. Furthermore, calcitriol blocked the HCV-induced expressions of apolipoprotein J and 78 kDa glucose-regulated protein, which was restored by pretreatment of kifunensine. These results indicated that the calcitriol-mediated HCV suppression was associated with the activation of VDR, interference with ERAD process, as well as blockades of PPAR, lipid accumulation and nitrative stress.

原文英語
文章編號57
期刊Viruses
10
發行號2
DOIs
出版狀態已發佈 - 二月 1 2018

指紋

Endoplasmic Reticulum-Associated Degradation
Peroxisome Proliferator-Activated Receptors
Calcitriol
Virus Diseases
Hepacivirus
Calcitriol Receptors
Nitric Oxide
Lipids
Clusterin
Linoleic Acid
Vitamin D
Hepatocellular Carcinoma

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

引用此文

Lin, Y. M., Sun, H. Y., Chiu, W. T., Su, H. C., Chien, Y. C., Chong, L. W., ... Tsao, C. W. (2018). Calcitriol inhibits HCV infection via blockade of activation of PPAR and interference with endoplasmic reticulum-associated degradation. Viruses, 10(2), [57]. https://doi.org/10.3390/v10020057

Calcitriol inhibits HCV infection via blockade of activation of PPAR and interference with endoplasmic reticulum-associated degradation. / Lin, Yu Min; Sun, Hung Yu; Chiu, Wen Tai; Su, Hui Chen; Chien, Yu Chieh; Chong, Lee Won; Chang, Hung Chuen; Bai, Chyi Huey; Young, Kung Chia; Tsao, Chiung Wen.

於: Viruses, 卷 10, 編號 2, 57, 01.02.2018.

研究成果: 雜誌貢獻文章

Lin, YM, Sun, HY, Chiu, WT, Su, HC, Chien, YC, Chong, LW, Chang, HC, Bai, CH, Young, KC & Tsao, CW 2018, 'Calcitriol inhibits HCV infection via blockade of activation of PPAR and interference with endoplasmic reticulum-associated degradation', Viruses, 卷 10, 編號 2, 57. https://doi.org/10.3390/v10020057
Lin, Yu Min ; Sun, Hung Yu ; Chiu, Wen Tai ; Su, Hui Chen ; Chien, Yu Chieh ; Chong, Lee Won ; Chang, Hung Chuen ; Bai, Chyi Huey ; Young, Kung Chia ; Tsao, Chiung Wen. / Calcitriol inhibits HCV infection via blockade of activation of PPAR and interference with endoplasmic reticulum-associated degradation. 於: Viruses. 2018 ; 卷 10, 編號 2.
@article{8c8eb97728ae43f2b29cc7d4c1802bd4,
title = "Calcitriol inhibits HCV infection via blockade of activation of PPAR and interference with endoplasmic reticulum-associated degradation",
abstract = "Vitamin D has been identified as an innate anti-hepatitis C virus (HCV) agent but the possible mechanisms for this issue remain unclear. Here, we clarified the mechanisms of calcitriol-mediated inhibition of HCV infection. Calcitriol partially inhibited HCV infection, nitric oxide (NO) release and lipid accumulation in Huh7.5 human hepatoma cells via the activation of vitamin D receptor (VDR). When cells were pretreated with the activators of peroxisome proliferator-activated receptor (PPAR)-α (Wy14643) and -γ (Ly171883), the calcitriol-mediated HCV suppression was reversed. Otherwise, three individual stimulators of PPAR-α/β/γ blocked the activation of VDR. PPAR-β (linoleic acid) reversed the inhibition of NO release, whereas PPAR-γ (Ly171883) reversed the inhibitions of NO release and lipid accumulation in the presence of calcitriol. The calcitriol-mediated viral suppression, inhibition of NO release and activation of VDR were partially blocked by an inhibitor of endoplasmic reticulum-associated degradation (ERAD), kifunensine. Furthermore, calcitriol blocked the HCV-induced expressions of apolipoprotein J and 78 kDa glucose-regulated protein, which was restored by pretreatment of kifunensine. These results indicated that the calcitriol-mediated HCV suppression was associated with the activation of VDR, interference with ERAD process, as well as blockades of PPAR, lipid accumulation and nitrative stress.",
keywords = "Calcitriol, Endoplasmic reticulum-associated degradation, Hepatitis C virus infection, Nitrative stress, Peroxisome proliferator-activated receptor",
author = "Lin, {Yu Min} and Sun, {Hung Yu} and Chiu, {Wen Tai} and Su, {Hui Chen} and Chien, {Yu Chieh} and Chong, {Lee Won} and Chang, {Hung Chuen} and Bai, {Chyi Huey} and Young, {Kung Chia} and Tsao, {Chiung Wen}",
year = "2018",
month = "2",
day = "1",
doi = "10.3390/v10020057",
language = "English",
volume = "10",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "2",

}

TY - JOUR

T1 - Calcitriol inhibits HCV infection via blockade of activation of PPAR and interference with endoplasmic reticulum-associated degradation

AU - Lin, Yu Min

AU - Sun, Hung Yu

AU - Chiu, Wen Tai

AU - Su, Hui Chen

AU - Chien, Yu Chieh

AU - Chong, Lee Won

AU - Chang, Hung Chuen

AU - Bai, Chyi Huey

AU - Young, Kung Chia

AU - Tsao, Chiung Wen

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Vitamin D has been identified as an innate anti-hepatitis C virus (HCV) agent but the possible mechanisms for this issue remain unclear. Here, we clarified the mechanisms of calcitriol-mediated inhibition of HCV infection. Calcitriol partially inhibited HCV infection, nitric oxide (NO) release and lipid accumulation in Huh7.5 human hepatoma cells via the activation of vitamin D receptor (VDR). When cells were pretreated with the activators of peroxisome proliferator-activated receptor (PPAR)-α (Wy14643) and -γ (Ly171883), the calcitriol-mediated HCV suppression was reversed. Otherwise, three individual stimulators of PPAR-α/β/γ blocked the activation of VDR. PPAR-β (linoleic acid) reversed the inhibition of NO release, whereas PPAR-γ (Ly171883) reversed the inhibitions of NO release and lipid accumulation in the presence of calcitriol. The calcitriol-mediated viral suppression, inhibition of NO release and activation of VDR were partially blocked by an inhibitor of endoplasmic reticulum-associated degradation (ERAD), kifunensine. Furthermore, calcitriol blocked the HCV-induced expressions of apolipoprotein J and 78 kDa glucose-regulated protein, which was restored by pretreatment of kifunensine. These results indicated that the calcitriol-mediated HCV suppression was associated with the activation of VDR, interference with ERAD process, as well as blockades of PPAR, lipid accumulation and nitrative stress.

AB - Vitamin D has been identified as an innate anti-hepatitis C virus (HCV) agent but the possible mechanisms for this issue remain unclear. Here, we clarified the mechanisms of calcitriol-mediated inhibition of HCV infection. Calcitriol partially inhibited HCV infection, nitric oxide (NO) release and lipid accumulation in Huh7.5 human hepatoma cells via the activation of vitamin D receptor (VDR). When cells were pretreated with the activators of peroxisome proliferator-activated receptor (PPAR)-α (Wy14643) and -γ (Ly171883), the calcitriol-mediated HCV suppression was reversed. Otherwise, three individual stimulators of PPAR-α/β/γ blocked the activation of VDR. PPAR-β (linoleic acid) reversed the inhibition of NO release, whereas PPAR-γ (Ly171883) reversed the inhibitions of NO release and lipid accumulation in the presence of calcitriol. The calcitriol-mediated viral suppression, inhibition of NO release and activation of VDR were partially blocked by an inhibitor of endoplasmic reticulum-associated degradation (ERAD), kifunensine. Furthermore, calcitriol blocked the HCV-induced expressions of apolipoprotein J and 78 kDa glucose-regulated protein, which was restored by pretreatment of kifunensine. These results indicated that the calcitriol-mediated HCV suppression was associated with the activation of VDR, interference with ERAD process, as well as blockades of PPAR, lipid accumulation and nitrative stress.

KW - Calcitriol

KW - Endoplasmic reticulum-associated degradation

KW - Hepatitis C virus infection

KW - Nitrative stress

KW - Peroxisome proliferator-activated receptor

UR - http://www.scopus.com/inward/record.url?scp=85041619536&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041619536&partnerID=8YFLogxK

U2 - 10.3390/v10020057

DO - 10.3390/v10020057

M3 - Article

VL - 10

JO - Viruses

JF - Viruses

SN - 1999-4915

IS - 2

M1 - 57

ER -