Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression
Background/Aim Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying in...
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| Veröffentlicht in: | Digestive diseases and sciences 2016-09, Vol.61 (9), p.2522-2534 |
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| container_title | Digestive diseases and sciences |
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| creator | Wang, Na Han, Qing Wang, Gai Ma, Wei-Ping Wang, Jia Wu, Wen-Xin Guo, Yu Liu, Li Jiang, Xiao-Yu Xie, Xiao-Li Jiang, Hui-Qing |
| description | Background/Aim
Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying intestinal epithelial dysfunction was evaluated both in vitro and in vivo.
Methods
Caco-2 cells (in vitro) and male Wistar rats (
n
= 60; in vivo) were used to evaluate the role of Res on intestinal epithelial dysfunction. Hydrogen peroxide was used to induce oxidative stress in the Caco-2 cells. In bile duct-ligated group, OJ was successfully established on Day 7 after bile duct ligation, whereas sham-operated and vehicle-treated rats served as controls. Western blot and RT-qPCR were performed to analyze TJ proteins expression in epithelium isolated from rat intestine.
Results
Intestinal hyperpermeability was associated with decreased expression and phosphorylation of occludin and zonula occluden (ZO-1), but increased oxidation in Caco-2 cells and the intestinal epithelium. Res treatment increased the epithelial expression and phosphorylation of occludin and ZO-1 in a concentration-dependent manner. Moreover, Res which protected Caco-2 cells from H
2
O
2
-induced oxidative damage clearly reduced malondialdehyde level and intracellular reactive oxygen species accumulation, but increased the expression levels of superoxide dismutase and heme oxygenase-1 (HO-1). Further studies showed that Res also inhibited H
2
O
2
-induced protein kinase C activity and p38 phosphorylation. Interestingly, these effects of Res were abolished by the HO-1 inhibitor zinc protoporphyrin or knockdown of HO-1 by siRNA.
Conclusions
Res protected gut barrier function possibly by initiating HO-1-dependent signaling which is essential for common expression of key tight junction proteins. It also provides a rationale to develop Res clinical applications of intestinal disorders. |
| doi_str_mv | 10.1007/s10620-016-4184-4 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1942219318</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A712939064</galeid><sourcerecordid>A712939064</sourcerecordid><originalsourceid>FETCH-LOGICAL-c538t-832f190777fbfbfcf86e0049da0eb24f4b5efea6e5a93136ccfd3f64c90518f03</originalsourceid><addsrcrecordid>eNqFkk9v1DAQxS0EokvhA3BBkbhwSfE4jpMcS1noSpWKgJ4txxkHV4kTbKfqnvniOGz5KxCag0ee33vyWI-Qp0BPgNLqZQAqGM0piJxDzXN-j2ygrIqclaK-TzZpkHoAcUQehXBNKW0qEA_JEauACw5sQ768x3CDXkU_Ddk7P0XUMWSXt7ZT0d5g9iF6DCHfuW7R2GU7FzFE69SQbWcbP-FgU_tKeW_RZ6_3wSxORzu5rN1nV7PHfhmSkeuzcxwx-e57dCpgDtn2dl6tE_uYPDBqCPjk7jwmV2-2H8_O84vLt7uz04tcl0Ud87pgBhpaVZVpU2lTC6SUN52i2DJueFuiQSWwVE0BhdDadIURXDe0hNrQ4pi8OPjOfvq8pD3kaIPGYVAOpyVIaDhjkLT1_9EagDVMVGVCn_-BXk-LTz_0jaKiBAb8J9WrAaV1Zope6dVUnlbJqmioWKmTv1CpOhytnhwam-5_E8BBoP0UgkcjZ29H5fcSqFwzIg8ZkSkKcs2IXDXP7h68tCN2PxTfQ5EAdgBCGrke_S8b_dP1K2UbxvI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1810651214</pqid></control><display><type>article</type><title>Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Wang, Na ; Han, Qing ; Wang, Gai ; Ma, Wei-Ping ; Wang, Jia ; Wu, Wen-Xin ; Guo, Yu ; Liu, Li ; Jiang, Xiao-Yu ; Xie, Xiao-Li ; Jiang, Hui-Qing</creator><creatorcontrib>Wang, Na ; Han, Qing ; Wang, Gai ; Ma, Wei-Ping ; Wang, Jia ; Wu, Wen-Xin ; Guo, Yu ; Liu, Li ; Jiang, Xiao-Yu ; Xie, Xiao-Li ; Jiang, Hui-Qing</creatorcontrib><description>Background/Aim
Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying intestinal epithelial dysfunction was evaluated both in vitro and in vivo.
Methods
Caco-2 cells (in vitro) and male Wistar rats (
n
= 60; in vivo) were used to evaluate the role of Res on intestinal epithelial dysfunction. Hydrogen peroxide was used to induce oxidative stress in the Caco-2 cells. In bile duct-ligated group, OJ was successfully established on Day 7 after bile duct ligation, whereas sham-operated and vehicle-treated rats served as controls. Western blot and RT-qPCR were performed to analyze TJ proteins expression in epithelium isolated from rat intestine.
Results
Intestinal hyperpermeability was associated with decreased expression and phosphorylation of occludin and zonula occluden (ZO-1), but increased oxidation in Caco-2 cells and the intestinal epithelium. Res treatment increased the epithelial expression and phosphorylation of occludin and ZO-1 in a concentration-dependent manner. Moreover, Res which protected Caco-2 cells from H
2
O
2
-induced oxidative damage clearly reduced malondialdehyde level and intracellular reactive oxygen species accumulation, but increased the expression levels of superoxide dismutase and heme oxygenase-1 (HO-1). Further studies showed that Res also inhibited H
2
O
2
-induced protein kinase C activity and p38 phosphorylation. Interestingly, these effects of Res were abolished by the HO-1 inhibitor zinc protoporphyrin or knockdown of HO-1 by siRNA.
Conclusions
Res protected gut barrier function possibly by initiating HO-1-dependent signaling which is essential for common expression of key tight junction proteins. It also provides a rationale to develop Res clinical applications of intestinal disorders.</description><identifier>ISSN: 0163-2116</identifier><identifier>EISSN: 1573-2568</identifier><identifier>DOI: 10.1007/s10620-016-4184-4</identifier><identifier>PMID: 27146412</identifier><identifier>CODEN: DDSCDJ</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Analysis ; Animals ; Antioxidants - pharmacology ; Bile Ducts - surgery ; Biochemistry ; Blotting, Western ; Caco-2 Cells ; Gastroenterology ; Gastrointestinal diseases ; Health aspects ; Heme ; Heme Oxygenase-1 - drug effects ; Heme Oxygenase-1 - genetics ; Heme Oxygenase-1 - metabolism ; Hepatology ; Humans ; Hydrogen peroxide ; Hydrogen Peroxide - metabolism ; In Vitro Techniques ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - metabolism ; Jaundice, Obstructive - genetics ; Jaundice, Obstructive - metabolism ; Ligation ; Male ; Malondialdehyde - metabolism ; Medicine ; Medicine & Public Health ; Occludin - drug effects ; Occludin - metabolism ; Oncology ; Original Article ; Oxidative stress ; Oxidative Stress - drug effects ; Permeability - drug effects ; Phosphorylation - drug effects ; Protein Kinase C - drug effects ; Protein Kinase C - metabolism ; Protein kinases ; Rats, Wistar ; Reactive Oxygen Species - metabolism ; Real-Time Polymerase Chain Reaction ; Resveratrol ; RNA, Messenger - drug effects ; RNA, Messenger - metabolism ; Stilbenes - pharmacology ; Superoxide ; Tight Junctions - drug effects ; Tight Junctions - metabolism ; Transplant Surgery ; Up-Regulation ; Zonula Occludens-1 Protein - drug effects ; Zonula Occludens-1 Protein - metabolism</subject><ispartof>Digestive diseases and sciences, 2016-09, Vol.61 (9), p.2522-2534</ispartof><rights>Springer Science+Business Media New York 2016</rights><rights>COPYRIGHT 2016 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-832f190777fbfbfcf86e0049da0eb24f4b5efea6e5a93136ccfd3f64c90518f03</citedby><cites>FETCH-LOGICAL-c538t-832f190777fbfbfcf86e0049da0eb24f4b5efea6e5a93136ccfd3f64c90518f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10620-016-4184-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10620-016-4184-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27146412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Na</creatorcontrib><creatorcontrib>Han, Qing</creatorcontrib><creatorcontrib>Wang, Gai</creatorcontrib><creatorcontrib>Ma, Wei-Ping</creatorcontrib><creatorcontrib>Wang, Jia</creatorcontrib><creatorcontrib>Wu, Wen-Xin</creatorcontrib><creatorcontrib>Guo, Yu</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Jiang, Xiao-Yu</creatorcontrib><creatorcontrib>Xie, Xiao-Li</creatorcontrib><creatorcontrib>Jiang, Hui-Qing</creatorcontrib><title>Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression</title><title>Digestive diseases and sciences</title><addtitle>Dig Dis Sci</addtitle><addtitle>Dig Dis Sci</addtitle><description>Background/Aim
Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying intestinal epithelial dysfunction was evaluated both in vitro and in vivo.
Methods
Caco-2 cells (in vitro) and male Wistar rats (
n
= 60; in vivo) were used to evaluate the role of Res on intestinal epithelial dysfunction. Hydrogen peroxide was used to induce oxidative stress in the Caco-2 cells. In bile duct-ligated group, OJ was successfully established on Day 7 after bile duct ligation, whereas sham-operated and vehicle-treated rats served as controls. Western blot and RT-qPCR were performed to analyze TJ proteins expression in epithelium isolated from rat intestine.
Results
Intestinal hyperpermeability was associated with decreased expression and phosphorylation of occludin and zonula occluden (ZO-1), but increased oxidation in Caco-2 cells and the intestinal epithelium. Res treatment increased the epithelial expression and phosphorylation of occludin and ZO-1 in a concentration-dependent manner. Moreover, Res which protected Caco-2 cells from H
2
O
2
-induced oxidative damage clearly reduced malondialdehyde level and intracellular reactive oxygen species accumulation, but increased the expression levels of superoxide dismutase and heme oxygenase-1 (HO-1). Further studies showed that Res also inhibited H
2
O
2
-induced protein kinase C activity and p38 phosphorylation. Interestingly, these effects of Res were abolished by the HO-1 inhibitor zinc protoporphyrin or knockdown of HO-1 by siRNA.
Conclusions
Res protected gut barrier function possibly by initiating HO-1-dependent signaling which is essential for common expression of key tight junction proteins. It also provides a rationale to develop Res clinical applications of intestinal disorders.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Bile Ducts - surgery</subject><subject>Biochemistry</subject><subject>Blotting, Western</subject><subject>Caco-2 Cells</subject><subject>Gastroenterology</subject><subject>Gastrointestinal diseases</subject><subject>Health aspects</subject><subject>Heme</subject><subject>Heme Oxygenase-1 - drug effects</subject><subject>Heme Oxygenase-1 - genetics</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Hydrogen peroxide</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>In Vitro Techniques</subject><subject>Intestinal Mucosa - drug effects</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Jaundice, Obstructive - genetics</subject><subject>Jaundice, Obstructive - metabolism</subject><subject>Ligation</subject><subject>Male</subject><subject>Malondialdehyde - metabolism</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Occludin - drug effects</subject><subject>Occludin - metabolism</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Permeability - drug effects</subject><subject>Phosphorylation - drug effects</subject><subject>Protein Kinase C - drug effects</subject><subject>Protein Kinase C - metabolism</subject><subject>Protein kinases</subject><subject>Rats, Wistar</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Resveratrol</subject><subject>RNA, Messenger - drug effects</subject><subject>RNA, Messenger - metabolism</subject><subject>Stilbenes - pharmacology</subject><subject>Superoxide</subject><subject>Tight Junctions - drug effects</subject><subject>Tight Junctions - metabolism</subject><subject>Transplant Surgery</subject><subject>Up-Regulation</subject><subject>Zonula Occludens-1 Protein - drug effects</subject><subject>Zonula Occludens-1 Protein - metabolism</subject><issn>0163-2116</issn><issn>1573-2568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkk9v1DAQxS0EokvhA3BBkbhwSfE4jpMcS1noSpWKgJ4txxkHV4kTbKfqnvniOGz5KxCag0ee33vyWI-Qp0BPgNLqZQAqGM0piJxDzXN-j2ygrIqclaK-TzZpkHoAcUQehXBNKW0qEA_JEauACw5sQ768x3CDXkU_Ddk7P0XUMWSXt7ZT0d5g9iF6DCHfuW7R2GU7FzFE69SQbWcbP-FgU_tKeW_RZ6_3wSxORzu5rN1nV7PHfhmSkeuzcxwx-e57dCpgDtn2dl6tE_uYPDBqCPjk7jwmV2-2H8_O84vLt7uz04tcl0Ud87pgBhpaVZVpU2lTC6SUN52i2DJueFuiQSWwVE0BhdDadIURXDe0hNrQ4pi8OPjOfvq8pD3kaIPGYVAOpyVIaDhjkLT1_9EagDVMVGVCn_-BXk-LTz_0jaKiBAb8J9WrAaV1Zope6dVUnlbJqmioWKmTv1CpOhytnhwam-5_E8BBoP0UgkcjZ29H5fcSqFwzIg8ZkSkKcs2IXDXP7h68tCN2PxTfQ5EAdgBCGrke_S8b_dP1K2UbxvI</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Wang, Na</creator><creator>Han, Qing</creator><creator>Wang, Gai</creator><creator>Ma, Wei-Ping</creator><creator>Wang, Jia</creator><creator>Wu, Wen-Xin</creator><creator>Guo, Yu</creator><creator>Liu, Li</creator><creator>Jiang, Xiao-Yu</creator><creator>Xie, Xiao-Li</creator><creator>Jiang, Hui-Qing</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20160901</creationdate><title>Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression</title><author>Wang, Na ; Han, Qing ; Wang, Gai ; Ma, Wei-Ping ; Wang, Jia ; Wu, Wen-Xin ; Guo, Yu ; Liu, Li ; Jiang, Xiao-Yu ; Xie, Xiao-Li ; Jiang, Hui-Qing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-832f190777fbfbfcf86e0049da0eb24f4b5efea6e5a93136ccfd3f64c90518f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Bile Ducts - surgery</topic><topic>Biochemistry</topic><topic>Blotting, Western</topic><topic>Caco-2 Cells</topic><topic>Gastroenterology</topic><topic>Gastrointestinal diseases</topic><topic>Health aspects</topic><topic>Heme</topic><topic>Heme Oxygenase-1 - drug effects</topic><topic>Heme Oxygenase-1 - genetics</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Hydrogen peroxide</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>In Vitro Techniques</topic><topic>Intestinal Mucosa - drug effects</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Jaundice, Obstructive - genetics</topic><topic>Jaundice, Obstructive - metabolism</topic><topic>Ligation</topic><topic>Male</topic><topic>Malondialdehyde - metabolism</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Occludin - drug effects</topic><topic>Occludin - metabolism</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Permeability - drug effects</topic><topic>Phosphorylation - drug effects</topic><topic>Protein Kinase C - drug effects</topic><topic>Protein Kinase C - metabolism</topic><topic>Protein kinases</topic><topic>Rats, Wistar</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Resveratrol</topic><topic>RNA, Messenger - drug effects</topic><topic>RNA, Messenger - metabolism</topic><topic>Stilbenes - pharmacology</topic><topic>Superoxide</topic><topic>Tight Junctions - drug effects</topic><topic>Tight Junctions - metabolism</topic><topic>Transplant Surgery</topic><topic>Up-Regulation</topic><topic>Zonula Occludens-1 Protein - drug effects</topic><topic>Zonula Occludens-1 Protein - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Na</creatorcontrib><creatorcontrib>Han, Qing</creatorcontrib><creatorcontrib>Wang, Gai</creatorcontrib><creatorcontrib>Ma, Wei-Ping</creatorcontrib><creatorcontrib>Wang, Jia</creatorcontrib><creatorcontrib>Wu, Wen-Xin</creatorcontrib><creatorcontrib>Guo, Yu</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Jiang, Xiao-Yu</creatorcontrib><creatorcontrib>Xie, Xiao-Li</creatorcontrib><creatorcontrib>Jiang, Hui-Qing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Digestive diseases and sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Na</au><au>Han, Qing</au><au>Wang, Gai</au><au>Ma, Wei-Ping</au><au>Wang, Jia</au><au>Wu, Wen-Xin</au><au>Guo, Yu</au><au>Liu, Li</au><au>Jiang, Xiao-Yu</au><au>Xie, Xiao-Li</au><au>Jiang, Hui-Qing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression</atitle><jtitle>Digestive diseases and sciences</jtitle><stitle>Dig Dis Sci</stitle><addtitle>Dig Dis Sci</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>61</volume><issue>9</issue><spage>2522</spage><epage>2534</epage><pages>2522-2534</pages><issn>0163-2116</issn><eissn>1573-2568</eissn><coden>DDSCDJ</coden><abstract>Background/Aim
Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying intestinal epithelial dysfunction was evaluated both in vitro and in vivo.
Methods
Caco-2 cells (in vitro) and male Wistar rats (
n
= 60; in vivo) were used to evaluate the role of Res on intestinal epithelial dysfunction. Hydrogen peroxide was used to induce oxidative stress in the Caco-2 cells. In bile duct-ligated group, OJ was successfully established on Day 7 after bile duct ligation, whereas sham-operated and vehicle-treated rats served as controls. Western blot and RT-qPCR were performed to analyze TJ proteins expression in epithelium isolated from rat intestine.
Results
Intestinal hyperpermeability was associated with decreased expression and phosphorylation of occludin and zonula occluden (ZO-1), but increased oxidation in Caco-2 cells and the intestinal epithelium. Res treatment increased the epithelial expression and phosphorylation of occludin and ZO-1 in a concentration-dependent manner. Moreover, Res which protected Caco-2 cells from H
2
O
2
-induced oxidative damage clearly reduced malondialdehyde level and intracellular reactive oxygen species accumulation, but increased the expression levels of superoxide dismutase and heme oxygenase-1 (HO-1). Further studies showed that Res also inhibited H
2
O
2
-induced protein kinase C activity and p38 phosphorylation. Interestingly, these effects of Res were abolished by the HO-1 inhibitor zinc protoporphyrin or knockdown of HO-1 by siRNA.
Conclusions
Res protected gut barrier function possibly by initiating HO-1-dependent signaling which is essential for common expression of key tight junction proteins. It also provides a rationale to develop Res clinical applications of intestinal disorders.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>27146412</pmid><doi>10.1007/s10620-016-4184-4</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0163-2116 |
| ispartof | Digestive diseases and sciences, 2016-09, Vol.61 (9), p.2522-2534 |
| issn | 0163-2116 1573-2568 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1942219318 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Analysis Animals Antioxidants - pharmacology Bile Ducts - surgery Biochemistry Blotting, Western Caco-2 Cells Gastroenterology Gastrointestinal diseases Health aspects Heme Heme Oxygenase-1 - drug effects Heme Oxygenase-1 - genetics Heme Oxygenase-1 - metabolism Hepatology Humans Hydrogen peroxide Hydrogen Peroxide - metabolism In Vitro Techniques Intestinal Mucosa - drug effects Intestinal Mucosa - metabolism Jaundice, Obstructive - genetics Jaundice, Obstructive - metabolism Ligation Male Malondialdehyde - metabolism Medicine Medicine & Public Health Occludin - drug effects Occludin - metabolism Oncology Original Article Oxidative stress Oxidative Stress - drug effects Permeability - drug effects Phosphorylation - drug effects Protein Kinase C - drug effects Protein Kinase C - metabolism Protein kinases Rats, Wistar Reactive Oxygen Species - metabolism Real-Time Polymerase Chain Reaction Resveratrol RNA, Messenger - drug effects RNA, Messenger - metabolism Stilbenes - pharmacology Superoxide Tight Junctions - drug effects Tight Junctions - metabolism Transplant Surgery Up-Regulation Zonula Occludens-1 Protein - drug effects Zonula Occludens-1 Protein - metabolism |
| title | Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T04%3A01%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Resveratrol%20Protects%20Oxidative%20Stress-Induced%20Intestinal%20Epithelial%20Barrier%20Dysfunction%20by%20Upregulating%20Heme%20Oxygenase-1%20Expression&rft.jtitle=Digestive%20diseases%20and%20sciences&rft.au=Wang,%20Na&rft.date=2016-09-01&rft.volume=61&rft.issue=9&rft.spage=2522&rft.epage=2534&rft.pages=2522-2534&rft.issn=0163-2116&rft.eissn=1573-2568&rft.coden=DDSCDJ&rft_id=info:doi/10.1007/s10620-016-4184-4&rft_dat=%3Cgale_proqu%3EA712939064%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1810651214&rft_id=info:pmid/27146412&rft_galeid=A712939064&rfr_iscdi=true |