All-Trans Retinoic Acid Attenuates Transmissible Gastroenteritis Virus-Induced Apoptosis in IPEC-J2 Cells via Inhibiting ROS-Mediated P<sub>38</sub>MAPK Signaling Pathway
Transmissible gastroenteritis virus (TGEV) can cause diarrhea, dehydration, and high mortality in piglets, which is closely related to intestinal epithelial cell apoptosis caused by TGEV infection. All-trans retinoic acid (ATRA) is the active metabolite of vitamin A, which has antioxidant and anti-a...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-02-01
|
Series: | Antioxidants |
Subjects: | |
Online Access: | https://www.mdpi.com/2076-3921/11/2/345 |
_version_ | 1797483175058866176 |
---|---|
author | Junning Pu Daiwen Chen Gang Tian Jun He Zhiqing Huang Ping Zheng Xiangbing Mao Jie Yu Junqiu Luo Yuheng Luo Hui Yan Bing Yu |
author_facet | Junning Pu Daiwen Chen Gang Tian Jun He Zhiqing Huang Ping Zheng Xiangbing Mao Jie Yu Junqiu Luo Yuheng Luo Hui Yan Bing Yu |
author_sort | Junning Pu |
collection | DOAJ |
description | Transmissible gastroenteritis virus (TGEV) can cause diarrhea, dehydration, and high mortality in piglets, which is closely related to intestinal epithelial cell apoptosis caused by TGEV infection. All-trans retinoic acid (ATRA) is the active metabolite of vitamin A, which has antioxidant and anti-apoptotic properties. However, it is unknown whether ATRA can attenuate TGEV-induced IPEC-J2 cells apoptosis. Therefore, we investigated the protective effects of ATRA on TGEV-induced apoptosis of IPEC-J2 cells and explored the potential molecular mechanism. Our results indicated that TGEV infection caused IPEC-J2 cells damage and apoptosis. However, ATRA treatment attenuated TGEV-induced IPEC-J2 cells damage by upregulating the mRNA expressions of ZO-1, Occludin, and Mucin-1. ATRA treatment also attenuated TGEV-induced apoptosis in IPEC-J2 cells by downregulating the expression of Caspase-3, which is related to the inhibition of death receptor (Fas and Caspase-8) and mitochondrial (Bax, Bcl-2, and Caspase-9) pathways. Moreover, ATRA treatment prevented TGEV-induced ROS and MDA production and the upregulation of P<sub>38</sub>MAPK phosphorylation level, which is related to the increase in the activities of antioxidant enzymes (SOD, CAT, and T-AOC) and the mRNA abundance of antioxidant-related genes (GPX1, GPX2, SOD1, CAT, GCLC, and GCLM). In addition, treatment of TGEV-infected IPEC-J2 cells with the ROS inhibitors (NAC) significantly reduced the protein levels of p-P<sub>38</sub>MAPK, Fas, Bax, and Cleaved-caspase-3 and the percentage of apoptotic cells. Our results indicated that ATRA attenuated TGEV-induced apoptosis in IPEC-J2 cells via improving the antioxidant capacity, thereby inhibiting the cell damage. the mechanism of which is associated with the inhibition of ROS-mediated P<sub>38</sub>MAPK signaling pathway. |
first_indexed | 2024-03-09T22:44:09Z |
format | Article |
id | doaj.art-0a73770fb42f4703a017c8c23654efca |
institution | Directory Open Access Journal |
issn | 2076-3921 |
language | English |
last_indexed | 2024-03-09T22:44:09Z |
publishDate | 2022-02-01 |
publisher | MDPI AG |
record_format | Article |
series | Antioxidants |
spelling | doaj.art-0a73770fb42f4703a017c8c23654efca2023-11-23T18:32:21ZengMDPI AGAntioxidants2076-39212022-02-0111234510.3390/antiox11020345All-Trans Retinoic Acid Attenuates Transmissible Gastroenteritis Virus-Induced Apoptosis in IPEC-J2 Cells via Inhibiting ROS-Mediated P<sub>38</sub>MAPK Signaling PathwayJunning Pu0Daiwen Chen1Gang Tian2Jun He3Zhiqing Huang4Ping Zheng5Xiangbing Mao6Jie Yu7Junqiu Luo8Yuheng Luo9Hui Yan10Bing Yu11Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, ChinaTransmissible gastroenteritis virus (TGEV) can cause diarrhea, dehydration, and high mortality in piglets, which is closely related to intestinal epithelial cell apoptosis caused by TGEV infection. All-trans retinoic acid (ATRA) is the active metabolite of vitamin A, which has antioxidant and anti-apoptotic properties. However, it is unknown whether ATRA can attenuate TGEV-induced IPEC-J2 cells apoptosis. Therefore, we investigated the protective effects of ATRA on TGEV-induced apoptosis of IPEC-J2 cells and explored the potential molecular mechanism. Our results indicated that TGEV infection caused IPEC-J2 cells damage and apoptosis. However, ATRA treatment attenuated TGEV-induced IPEC-J2 cells damage by upregulating the mRNA expressions of ZO-1, Occludin, and Mucin-1. ATRA treatment also attenuated TGEV-induced apoptosis in IPEC-J2 cells by downregulating the expression of Caspase-3, which is related to the inhibition of death receptor (Fas and Caspase-8) and mitochondrial (Bax, Bcl-2, and Caspase-9) pathways. Moreover, ATRA treatment prevented TGEV-induced ROS and MDA production and the upregulation of P<sub>38</sub>MAPK phosphorylation level, which is related to the increase in the activities of antioxidant enzymes (SOD, CAT, and T-AOC) and the mRNA abundance of antioxidant-related genes (GPX1, GPX2, SOD1, CAT, GCLC, and GCLM). In addition, treatment of TGEV-infected IPEC-J2 cells with the ROS inhibitors (NAC) significantly reduced the protein levels of p-P<sub>38</sub>MAPK, Fas, Bax, and Cleaved-caspase-3 and the percentage of apoptotic cells. Our results indicated that ATRA attenuated TGEV-induced apoptosis in IPEC-J2 cells via improving the antioxidant capacity, thereby inhibiting the cell damage. the mechanism of which is associated with the inhibition of ROS-mediated P<sub>38</sub>MAPK signaling pathway.https://www.mdpi.com/2076-3921/11/2/345all-trans retinoic acidtransmissible gastroenteritis virusapoptosisoxidative stressROS/P<sub>38</sub>MAPK pathwayIPEC-J2 cells |
spellingShingle | Junning Pu Daiwen Chen Gang Tian Jun He Zhiqing Huang Ping Zheng Xiangbing Mao Jie Yu Junqiu Luo Yuheng Luo Hui Yan Bing Yu All-Trans Retinoic Acid Attenuates Transmissible Gastroenteritis Virus-Induced Apoptosis in IPEC-J2 Cells via Inhibiting ROS-Mediated P<sub>38</sub>MAPK Signaling Pathway Antioxidants all-trans retinoic acid transmissible gastroenteritis virus apoptosis oxidative stress ROS/P<sub>38</sub>MAPK pathway IPEC-J2 cells |
title | All-Trans Retinoic Acid Attenuates Transmissible Gastroenteritis Virus-Induced Apoptosis in IPEC-J2 Cells via Inhibiting ROS-Mediated P<sub>38</sub>MAPK Signaling Pathway |
title_full | All-Trans Retinoic Acid Attenuates Transmissible Gastroenteritis Virus-Induced Apoptosis in IPEC-J2 Cells via Inhibiting ROS-Mediated P<sub>38</sub>MAPK Signaling Pathway |
title_fullStr | All-Trans Retinoic Acid Attenuates Transmissible Gastroenteritis Virus-Induced Apoptosis in IPEC-J2 Cells via Inhibiting ROS-Mediated P<sub>38</sub>MAPK Signaling Pathway |
title_full_unstemmed | All-Trans Retinoic Acid Attenuates Transmissible Gastroenteritis Virus-Induced Apoptosis in IPEC-J2 Cells via Inhibiting ROS-Mediated P<sub>38</sub>MAPK Signaling Pathway |
title_short | All-Trans Retinoic Acid Attenuates Transmissible Gastroenteritis Virus-Induced Apoptosis in IPEC-J2 Cells via Inhibiting ROS-Mediated P<sub>38</sub>MAPK Signaling Pathway |
title_sort | all trans retinoic acid attenuates transmissible gastroenteritis virus induced apoptosis in ipec j2 cells via inhibiting ros mediated p sub 38 sub mapk signaling pathway |
topic | all-trans retinoic acid transmissible gastroenteritis virus apoptosis oxidative stress ROS/P<sub>38</sub>MAPK pathway IPEC-J2 cells |
url | https://www.mdpi.com/2076-3921/11/2/345 |
work_keys_str_mv | AT junningpu alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT daiwenchen alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT gangtian alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT junhe alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT zhiqinghuang alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT pingzheng alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT xiangbingmao alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT jieyu alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT junqiuluo alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT yuhengluo alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT huiyan alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway AT bingyu alltransretinoicacidattenuatestransmissiblegastroenteritisvirusinducedapoptosisinipecj2cellsviainhibitingrosmediatedpsub38submapksignalingpathway |