Tiron ameliorates high glucose‐induced cardiac myocyte apoptosis by PKCδ‐dependent inhibition of osteopontin
Summary Tiron functions as an effective antioxidant alleviating the intracellular reactive oxygen species (ROS) or the acute toxic metal overload. Previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (STZ)‐induced diabetic...
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| Veröffentlicht in: | Clinical and experimental pharmacology & physiology 2017-07, Vol.44 (7), p.760-770 |
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| container_title | Clinical and experimental pharmacology & physiology |
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| creator | Jiang, Ping Zhang, Deling Qiu, Hong Yi, Xianqi Zhang, Yemin Cao, Yingkang Zhao, Bo Xia, Zhongyuan Wang, Changhua |
| description | Summary
Tiron functions as an effective antioxidant alleviating the intracellular reactive oxygen species (ROS) or the acute toxic metal overload. Previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (STZ)‐induced diabetic rats, primary neonatal rat cardiomyocytes (NRVMs), and H9c2 embryonic rat cardiomyocytes. However, the underlying signalling mechanism is ill‐defined. In the present study, we found that tiron supplementation significantly inhibited apoptosis of high glucose (HG)‐treated NRVMs and the left ventricular cardiomyocytes from STZ‐diabetic rat, accompanied with a reduction of osteopontin (OPN) levels as well as an inhibition of PKCδ phosphorylation. OPN knockdown protected NRVMs against HG‐induced cell apoptosis. In addition, genetic inhibition of PKCδ mitigated HG‐stimulated enhancement of intracellular OPN levels in NRVMs. These findings indicate that ROS‐mediated activation of PKCδ upregulated OPN expression, leading to cardiac myocyte apoptosis. Interfering with ROS/PKCδ pathway by antioxidants such as tiron provides an optional therapeutic strategy for treatment and prevention of apoptosis‐related cardiovascular diseases including diabetic cardiomyopathy. |
| doi_str_mv | 10.1111/1440-1681.12762 |
| format | Article |
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Tiron functions as an effective antioxidant alleviating the intracellular reactive oxygen species (ROS) or the acute toxic metal overload. Previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (STZ)‐induced diabetic rats, primary neonatal rat cardiomyocytes (NRVMs), and H9c2 embryonic rat cardiomyocytes. However, the underlying signalling mechanism is ill‐defined. In the present study, we found that tiron supplementation significantly inhibited apoptosis of high glucose (HG)‐treated NRVMs and the left ventricular cardiomyocytes from STZ‐diabetic rat, accompanied with a reduction of osteopontin (OPN) levels as well as an inhibition of PKCδ phosphorylation. OPN knockdown protected NRVMs against HG‐induced cell apoptosis. In addition, genetic inhibition of PKCδ mitigated HG‐stimulated enhancement of intracellular OPN levels in NRVMs. These findings indicate that ROS‐mediated activation of PKCδ upregulated OPN expression, leading to cardiac myocyte apoptosis. Interfering with ROS/PKCδ pathway by antioxidants such as tiron provides an optional therapeutic strategy for treatment and prevention of apoptosis‐related cardiovascular diseases including diabetic cardiomyopathy.</description><identifier>ISSN: 0305-1870</identifier><identifier>EISSN: 1440-1681</identifier><identifier>DOI: 10.1111/1440-1681.12762</identifier><identifier>PMID: 28394420</identifier><language>eng</language><publisher>Australia</publisher><subject>1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology ; Animals ; apoptosis ; Apoptosis - drug effects ; cardiomyocytes ; Cell Line ; Diabetes Mellitus, Experimental - pathology ; Dose-Response Relationship, Drug ; Glucose - pharmacology ; Male ; Mice ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - pathology ; osteopontin ; Osteopontin - antagonists & inhibitors ; Phosphorylation - drug effects ; protein kinase C δ ; Protein Kinase C-delta - metabolism ; Rats ; tiron</subject><ispartof>Clinical and experimental pharmacology & physiology, 2017-07, Vol.44 (7), p.760-770</ispartof><rights>2017 John Wiley & Sons Australia, Ltd</rights><rights>2017 John Wiley & Sons Australia, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3432-b7d32ec5e04dba1743675f3c10fd24ccddd7f1634ab1ebcc79818f0c5c8536983</citedby><cites>FETCH-LOGICAL-c3432-b7d32ec5e04dba1743675f3c10fd24ccddd7f1634ab1ebcc79818f0c5c8536983</cites><orcidid>0000-0003-2817-2552</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2F1440-1681.12762$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2F1440-1681.12762$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28394420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Ping</creatorcontrib><creatorcontrib>Zhang, Deling</creatorcontrib><creatorcontrib>Qiu, Hong</creatorcontrib><creatorcontrib>Yi, Xianqi</creatorcontrib><creatorcontrib>Zhang, Yemin</creatorcontrib><creatorcontrib>Cao, Yingkang</creatorcontrib><creatorcontrib>Zhao, Bo</creatorcontrib><creatorcontrib>Xia, Zhongyuan</creatorcontrib><creatorcontrib>Wang, Changhua</creatorcontrib><title>Tiron ameliorates high glucose‐induced cardiac myocyte apoptosis by PKCδ‐dependent inhibition of osteopontin</title><title>Clinical and experimental pharmacology & physiology</title><addtitle>Clin Exp Pharmacol Physiol</addtitle><description>Summary
Tiron functions as an effective antioxidant alleviating the intracellular reactive oxygen species (ROS) or the acute toxic metal overload. Previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (STZ)‐induced diabetic rats, primary neonatal rat cardiomyocytes (NRVMs), and H9c2 embryonic rat cardiomyocytes. However, the underlying signalling mechanism is ill‐defined. In the present study, we found that tiron supplementation significantly inhibited apoptosis of high glucose (HG)‐treated NRVMs and the left ventricular cardiomyocytes from STZ‐diabetic rat, accompanied with a reduction of osteopontin (OPN) levels as well as an inhibition of PKCδ phosphorylation. OPN knockdown protected NRVMs against HG‐induced cell apoptosis. In addition, genetic inhibition of PKCδ mitigated HG‐stimulated enhancement of intracellular OPN levels in NRVMs. These findings indicate that ROS‐mediated activation of PKCδ upregulated OPN expression, leading to cardiac myocyte apoptosis. Interfering with ROS/PKCδ pathway by antioxidants such as tiron provides an optional therapeutic strategy for treatment and prevention of apoptosis‐related cardiovascular diseases including diabetic cardiomyopathy.</description><subject>1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology</subject><subject>Animals</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>cardiomyocytes</subject><subject>Cell Line</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Glucose - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>Myocytes, Cardiac - cytology</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - pathology</subject><subject>osteopontin</subject><subject>Osteopontin - antagonists & inhibitors</subject><subject>Phosphorylation - drug effects</subject><subject>protein kinase C δ</subject><subject>Protein Kinase C-delta - metabolism</subject><subject>Rats</subject><subject>tiron</subject><issn>0305-1870</issn><issn>1440-1681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtOwzAQQC0EoqWwZod8gbR27Hy6RFH5iEp0UdaRM560Rkkc4lQoO47AYTgHh-AkpAS6ZTYjjd68xSPkkrMp72fGpWQeD2M-5X4U-kdkfLgckzETLPB4HLEROXPumTEWsFCckpEfi7mUPhuTl7VpbEVViYWxjWrR0a3ZbOmm2IF1-PX2biq9A9QUVKONAlp2FroWqapt3VpnHM06unpIPj96WGONlcaqpabamsy0ppfbnFrXoq1t1ZrqnJzkqnB48bsn5OlmsU7uvOXj7X1yvfRASOF7WaSFjxAgkzpTPJIijIJcAGe59iWA1jrKeSikyjhmANE85nHOIIA4EOE8FhMyG7zQWOcazNO6MaVqupSzdB8v3adK96nSn3j9x9XwUe-yEvWB_6vVA8EAvJoCu_98abJYDeJvqOp-eg</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>Jiang, Ping</creator><creator>Zhang, Deling</creator><creator>Qiu, Hong</creator><creator>Yi, Xianqi</creator><creator>Zhang, Yemin</creator><creator>Cao, Yingkang</creator><creator>Zhao, Bo</creator><creator>Xia, Zhongyuan</creator><creator>Wang, Changhua</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-2817-2552</orcidid></search><sort><creationdate>201707</creationdate><title>Tiron ameliorates high glucose‐induced cardiac myocyte apoptosis by PKCδ‐dependent inhibition of osteopontin</title><author>Jiang, Ping ; Zhang, Deling ; Qiu, Hong ; Yi, Xianqi ; Zhang, Yemin ; Cao, Yingkang ; Zhao, Bo ; Xia, Zhongyuan ; Wang, Changhua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3432-b7d32ec5e04dba1743675f3c10fd24ccddd7f1634ab1ebcc79818f0c5c8536983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology</topic><topic>Animals</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>cardiomyocytes</topic><topic>Cell Line</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Glucose - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>Myocytes, Cardiac - cytology</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - pathology</topic><topic>osteopontin</topic><topic>Osteopontin - antagonists & inhibitors</topic><topic>Phosphorylation - drug effects</topic><topic>protein kinase C δ</topic><topic>Protein Kinase C-delta - metabolism</topic><topic>Rats</topic><topic>tiron</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Ping</creatorcontrib><creatorcontrib>Zhang, Deling</creatorcontrib><creatorcontrib>Qiu, Hong</creatorcontrib><creatorcontrib>Yi, Xianqi</creatorcontrib><creatorcontrib>Zhang, Yemin</creatorcontrib><creatorcontrib>Cao, Yingkang</creatorcontrib><creatorcontrib>Zhao, Bo</creatorcontrib><creatorcontrib>Xia, Zhongyuan</creatorcontrib><creatorcontrib>Wang, Changhua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Clinical and experimental pharmacology & physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Ping</au><au>Zhang, Deling</au><au>Qiu, Hong</au><au>Yi, Xianqi</au><au>Zhang, Yemin</au><au>Cao, Yingkang</au><au>Zhao, Bo</au><au>Xia, Zhongyuan</au><au>Wang, Changhua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tiron ameliorates high glucose‐induced cardiac myocyte apoptosis by PKCδ‐dependent inhibition of osteopontin</atitle><jtitle>Clinical and experimental pharmacology & physiology</jtitle><addtitle>Clin Exp Pharmacol Physiol</addtitle><date>2017-07</date><risdate>2017</risdate><volume>44</volume><issue>7</issue><spage>760</spage><epage>770</epage><pages>760-770</pages><issn>0305-1870</issn><eissn>1440-1681</eissn><abstract>Summary
Tiron functions as an effective antioxidant alleviating the intracellular reactive oxygen species (ROS) or the acute toxic metal overload. Previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (STZ)‐induced diabetic rats, primary neonatal rat cardiomyocytes (NRVMs), and H9c2 embryonic rat cardiomyocytes. However, the underlying signalling mechanism is ill‐defined. In the present study, we found that tiron supplementation significantly inhibited apoptosis of high glucose (HG)‐treated NRVMs and the left ventricular cardiomyocytes from STZ‐diabetic rat, accompanied with a reduction of osteopontin (OPN) levels as well as an inhibition of PKCδ phosphorylation. OPN knockdown protected NRVMs against HG‐induced cell apoptosis. In addition, genetic inhibition of PKCδ mitigated HG‐stimulated enhancement of intracellular OPN levels in NRVMs. These findings indicate that ROS‐mediated activation of PKCδ upregulated OPN expression, leading to cardiac myocyte apoptosis. Interfering with ROS/PKCδ pathway by antioxidants such as tiron provides an optional therapeutic strategy for treatment and prevention of apoptosis‐related cardiovascular diseases including diabetic cardiomyopathy.</abstract><cop>Australia</cop><pmid>28394420</pmid><doi>10.1111/1440-1681.12762</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2817-2552</orcidid></addata></record> |
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| subjects | 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology Animals apoptosis Apoptosis - drug effects cardiomyocytes Cell Line Diabetes Mellitus, Experimental - pathology Dose-Response Relationship, Drug Glucose - pharmacology Male Mice Myocytes, Cardiac - cytology Myocytes, Cardiac - drug effects Myocytes, Cardiac - pathology osteopontin Osteopontin - antagonists & inhibitors Phosphorylation - drug effects protein kinase C δ Protein Kinase C-delta - metabolism Rats tiron |
| title | Tiron ameliorates high glucose‐induced cardiac myocyte apoptosis by PKCδ‐dependent inhibition of osteopontin |
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