Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation
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 l...
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doaj-32731d06e42f41559fff306bb566d6cf2020-11-25T01:28:24ZengMDPI AGViruses1999-49152018-01-011025710.3390/v10020057v10020057Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated DegradationYu-Min Lin0Hung-Yu Sun1Wen-Tai Chiu2Hui-Chen Su3Yu-Chieh Chien4Lee-Won Chong5Hung-Chuen Chang6Chyi-Huey Bai7Kung-Chia Young8Chiung-Wen Tsao9Department of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Pharmacy, Chi-Mei Medical Center, Tainan 71004, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDepartment of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, TaiwanDepartment of Public Health, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDepartment of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Long Term Care, Chung Hwa University of Medical Technology, Tainan 71703, TaiwanVitamin 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.http://www.mdpi.com/1999-4915/10/2/57calcitriolhepatitis C virus infectionperoxisome proliferator-activated receptorendoplasmic reticulum-associated degradationnitrative stress |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation Viruses calcitriol hepatitis C virus infection peroxisome proliferator-activated receptor endoplasmic reticulum-associated degradation nitrative stress |
author_facet |
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 |
author_sort |
Yu-Min Lin |
title |
Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation |
title_short |
Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation |
title_full |
Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation |
title_fullStr |
Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation |
title_full_unstemmed |
Calcitriol Inhibits HCV Infection via Blockade of Activation of PPAR and Interference with Endoplasmic Reticulum-Associated Degradation |
title_sort |
calcitriol inhibits hcv infection via blockade of activation of ppar and interference with endoplasmic reticulum-associated degradation |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2018-01-01 |
description |
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. |
topic |
calcitriol hepatitis C virus infection peroxisome proliferator-activated receptor endoplasmic reticulum-associated degradation nitrative stress |
url |
http://www.mdpi.com/1999-4915/10/2/57 |
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