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Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury through PI3K/Akt-Mediated Nrf2 Signaling Pathway.
Oxid Med Cell Longev. 2019; 2019:7591840.OM

Abstract

Oxidative stress is implicated in a wide range of intestinal disorders and closely associated with their pathological processes. Resveratrol (RSV), a plant extract, plays a vital role in protecting various organs in vitro and in vivo. However, the benefits of RSV are controversial, and underlying mechanisms for its antioxidant effects on intestinal epithelial cells remain unclear. In this study, we evaluated the effects of RSV on oxidative stress induced by H2O2 in IPEC-J2 cells. We found that pretreatment with RSV significantly increased cell viability; increased expression levels of tight junction (TJ) proteins (claudin-1, occludin, and ZO-1); improved activities of superoxide dismutase-1 (SOD-1), catalase (CAT), and glutathione peroxidase (GSH-Px); and decreased intracellular reactive oxygen species (ROS) levels and apoptosis induced by H2O2 (P < 0.05). In addition, RSV upregulated Akt phosphorylation, Nrf2 phosphorylation, and expression levels of antioxidant genes HO-1, SOD-1, and CAT in a dose-dependent manner (P < 0.05) under oxidative stress. Knockdown of Nrf2 by short-hairpin RNA (shRNA) abrogated RSV-mediated protection against H2O2-induced apoptosis, RSV-induced increase of TJ protein levels, and antioxidant gene expression (SOD-1, CAT, and GSH-Px) (P < 0.05). Consistent with Nrf2 knockdown, the PI3K/Akt inhibitor LY294002 significantly suppressed RSV-induced Nrf2 phosphorylation and RSV-induced increase of TJ protein levels and antioxidant gene expression under H2O2 treatment (P < 0.05). Collectively, these results demonstrate that RSV can directly protect IPEC-J2 cells against oxidative stress through the PI3K/Akt-mediated Nrf2 signaling pathway, suggesting that RSV may be an effective feed additive against intestinal damage in livestock production.

Authors+Show Affiliations

Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, School of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, China. Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, 330045 Jiangxi, China.Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, School of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, China.Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, School of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, China.Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, School of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, China.Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, School of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, China.Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, School of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, China. Human Engineering & Research Center of Animal and Poultry Science, Key Lab Agroecology Processing Subtropical Region, Scientific Observational and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Science, Changsha, 410125 Hunan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31885814

Citation

Zhuang, Yu, et al. "Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury Through PI3K/Akt-Mediated Nrf2 Signaling Pathway." Oxidative Medicine and Cellular Longevity, vol. 2019, 2019, p. 7591840.
Zhuang Y, Wu H, Wang X, et al. Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury through PI3K/Akt-Mediated Nrf2 Signaling Pathway. Oxid Med Cell Longev. 2019;2019:7591840.
Zhuang, Y., Wu, H., Wang, X., He, J., He, S., & Yin, Y. (2019). Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury through PI3K/Akt-Mediated Nrf2 Signaling Pathway. Oxidative Medicine and Cellular Longevity, 2019, 7591840. https://doi.org/10.1155/2019/7591840
Zhuang Y, et al. Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury Through PI3K/Akt-Mediated Nrf2 Signaling Pathway. Oxid Med Cell Longev. 2019;2019:7591840. PubMed PMID: 31885814.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury through PI3K/Akt-Mediated Nrf2 Signaling Pathway. AU - Zhuang,Yu, AU - Wu,Huirong, AU - Wang,Xiangxiang, AU - He,Jieyu, AU - He,Shanping, AU - Yin,Yulong, Y1 - 2019/12/02/ PY - 2019/03/10/received PY - 2019/07/31/revised PY - 2019/11/05/accepted PY - 2019/12/31/entrez PY - 2019/12/31/pubmed PY - 2020/6/26/medline SP - 7591840 EP - 7591840 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2019 N2 - Oxidative stress is implicated in a wide range of intestinal disorders and closely associated with their pathological processes. Resveratrol (RSV), a plant extract, plays a vital role in protecting various organs in vitro and in vivo. However, the benefits of RSV are controversial, and underlying mechanisms for its antioxidant effects on intestinal epithelial cells remain unclear. In this study, we evaluated the effects of RSV on oxidative stress induced by H2O2 in IPEC-J2 cells. We found that pretreatment with RSV significantly increased cell viability; increased expression levels of tight junction (TJ) proteins (claudin-1, occludin, and ZO-1); improved activities of superoxide dismutase-1 (SOD-1), catalase (CAT), and glutathione peroxidase (GSH-Px); and decreased intracellular reactive oxygen species (ROS) levels and apoptosis induced by H2O2 (P < 0.05). In addition, RSV upregulated Akt phosphorylation, Nrf2 phosphorylation, and expression levels of antioxidant genes HO-1, SOD-1, and CAT in a dose-dependent manner (P < 0.05) under oxidative stress. Knockdown of Nrf2 by short-hairpin RNA (shRNA) abrogated RSV-mediated protection against H2O2-induced apoptosis, RSV-induced increase of TJ protein levels, and antioxidant gene expression (SOD-1, CAT, and GSH-Px) (P < 0.05). Consistent with Nrf2 knockdown, the PI3K/Akt inhibitor LY294002 significantly suppressed RSV-induced Nrf2 phosphorylation and RSV-induced increase of TJ protein levels and antioxidant gene expression under H2O2 treatment (P < 0.05). Collectively, these results demonstrate that RSV can directly protect IPEC-J2 cells against oxidative stress through the PI3K/Akt-mediated Nrf2 signaling pathway, suggesting that RSV may be an effective feed additive against intestinal damage in livestock production. SN - 1942-0994 UR - https://www.unboundmedicine.com/medline/citation/31885814/Resveratrol_Attenuates_Oxidative_Stress_Induced_Intestinal_Barrier_Injury_through_PI3K/Akt_Mediated_Nrf2_Signaling_Pathway_ L2 - https://doi.org/10.1155/2019/7591840 DB - PRIME DP - Unbound Medicine ER -