Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis
Curcumin is a natural polyphenol and is supposed to possess antioxidant, anti-inflammatory, anticancer, and antiapoptotic properties. Although some studies have reported the therapeutic effects of curcumin on ulcerative colitis (UC), the specific mechanism remains unclear. An in vitro coculture mode...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2021/5570796 |
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| author | Xinxin Zhou Mengting Ren Jinpu Yang Hanghai Pan Mosang Yu Feng Ji |
| author_facet | Xinxin Zhou Mengting Ren Jinpu Yang Hanghai Pan Mosang Yu Feng Ji |
| author_sort | Xinxin Zhou |
| collection | DOAJ |
| description | Curcumin is a natural polyphenol and is supposed to possess antioxidant, anti-inflammatory, anticancer, and antiapoptotic properties. Although some studies have reported the therapeutic effects of curcumin on ulcerative colitis (UC), the specific mechanism remains unclear. An in vitro coculture model of Caco-2 and differentiated THP-1 cells was established. After administration of curcumin (10 μM), Western blot analysis was performed to evaluate the protein levels of tight junction (TJ) proteins zonula occludens- (ZO-) 1 and claudin-1. Annexin V-APC/7-AAD assays and flow cytometry were conducted to assess Caco-2 cell apoptosis. The expression levels of oxidative stress and endoplasmic reticulum stress- (ERS-) related molecules were determined by Western blot analysis. Curcumin administration significantly upregulated ZO-1 and claudin-1 protein levels and reduced Caco-2 cell apoptosis. The protein levels of oxidative stress markers inducible nitric oxide synthase (iNOS) and γH2AX and ERS-induced apoptosis-related molecules C/EBP homologous protein (CHOP) and cleaved caspase-12 were significantly downregulated upon curcumin treatment. Furthermore, curcumin administration greatly blocked the protein kinase-like endoplasmic reticulum kinase- (PERK-) eukaryotic translation initiation factor 2α- (eIF2α-) activating transcription factor 4- (ATF4-) CHOP signaling pathway. Curcumin enhanced intestinal epithelial barrier integrity in the in vitro coculture model by upregulating TJ protein expressions and reducing intestinal epithelial cell apoptosis. The potential mechanisms may be suppression of ERS and subsequent apoptosis. |
| format | Article |
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| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Gastroenterology Research and Practice |
| spelling | doaj-art-df3cb92333434a31b9392a479bbc35a92025-02-03T01:25:18ZengWileyGastroenterology Research and Practice1687-61211687-630X2021-01-01202110.1155/2021/55707965570796Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent ApoptosisXinxin Zhou0Mengting Ren1Jinpu Yang2Hanghai Pan3Mosang Yu4Feng Ji5Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Gastroenterology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province, ChinaDepartment of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaDepartment of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, ChinaCurcumin is a natural polyphenol and is supposed to possess antioxidant, anti-inflammatory, anticancer, and antiapoptotic properties. Although some studies have reported the therapeutic effects of curcumin on ulcerative colitis (UC), the specific mechanism remains unclear. An in vitro coculture model of Caco-2 and differentiated THP-1 cells was established. After administration of curcumin (10 μM), Western blot analysis was performed to evaluate the protein levels of tight junction (TJ) proteins zonula occludens- (ZO-) 1 and claudin-1. Annexin V-APC/7-AAD assays and flow cytometry were conducted to assess Caco-2 cell apoptosis. The expression levels of oxidative stress and endoplasmic reticulum stress- (ERS-) related molecules were determined by Western blot analysis. Curcumin administration significantly upregulated ZO-1 and claudin-1 protein levels and reduced Caco-2 cell apoptosis. The protein levels of oxidative stress markers inducible nitric oxide synthase (iNOS) and γH2AX and ERS-induced apoptosis-related molecules C/EBP homologous protein (CHOP) and cleaved caspase-12 were significantly downregulated upon curcumin treatment. Furthermore, curcumin administration greatly blocked the protein kinase-like endoplasmic reticulum kinase- (PERK-) eukaryotic translation initiation factor 2α- (eIF2α-) activating transcription factor 4- (ATF4-) CHOP signaling pathway. Curcumin enhanced intestinal epithelial barrier integrity in the in vitro coculture model by upregulating TJ protein expressions and reducing intestinal epithelial cell apoptosis. The potential mechanisms may be suppression of ERS and subsequent apoptosis.http://dx.doi.org/10.1155/2021/5570796 |
| spellingShingle | Xinxin Zhou Mengting Ren Jinpu Yang Hanghai Pan Mosang Yu Feng Ji Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis Gastroenterology Research and Practice |
| title | Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis |
| title_full | Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis |
| title_fullStr | Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis |
| title_full_unstemmed | Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis |
| title_short | Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis |
| title_sort | curcumin improves epithelial barrier integrity of caco 2 monolayers by inhibiting endoplasmic reticulum stress and subsequent apoptosis |
| url | http://dx.doi.org/10.1155/2021/5570796 |
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