Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca2+ Homeostasis in Rat Heart
Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca 2+ Homeostasis in Rat Heart Nazmi Yaras 1 , Mehmet Ugur 1 , Semir Ozdemir 1 , Hakan Gurdal 2 , Nuhan Purali 3 , Alain Lacampagne 4 , Guy Vassort 4 and Belma Turan 1 1 Department of Biophysics, School of Medicine, Ankara Unive...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2005-11, Vol.54 (11), p.3082-3088 |
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| creator | YARAS, Nazmi UGUR, Mehmet OZDEMIR, Semir GURDAL, Hakan PURALI, Nuhan LACAMPAGNE, Alain VASSORT, Guy TURAN, Belma |
| description | Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca 2+ Homeostasis in Rat Heart
Nazmi Yaras 1 ,
Mehmet Ugur 1 ,
Semir Ozdemir 1 ,
Hakan Gurdal 2 ,
Nuhan Purali 3 ,
Alain Lacampagne 4 ,
Guy Vassort 4 and
Belma Turan 1
1 Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey
2 Department of Pharmacology, School of Medicine, Ankara University, Ankara, Turkey
3 Department of Biophysics, School of Medicine, Hacettepe University, Ankara, Turkey
4 INSERM U-637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, Montpellier, France
Address correspondence and reprint requests to Dr. Belma Turan, Department of Biophysics, School of Medicine, Ankara University,
Ankara, Turkey. E-mail: belma.turan{at}medicine.ankara.edu.tr
Abstract
The defects identified in the mechanical activity of the hearts from type 1 diabetic animals include alteration of Ca 2+ signaling via changes in critical processes that regulate intracellular Ca 2+ concentration. These defects result partially from a dysfunction of cardiac ryanodine receptor calcium release channel (RyR2).
The present study was designed to determine whether the properties of the Ca 2+ sparks might provide insight into the role of RyR2 in the altered Ca 2+ signaling in cardiomyocytes from diabetic animals when they were analyzed together with Ca 2+ transients. Basal Ca 2+ level as well as Ca 2+ -spark frequency of cardiomyoctes isolated from 5-week streptozotocin (STZ)-induced diabetic rats significantly increased
with respect to aged-matched control rats. Ca 2+ transients exhibited significantly reduced amplitude and prolonged time courses as well as depressed Ca 2+ loading of sarcoplasmic reticulum in diabetic rats. Spatio-temporal properties of the Ca 2+ sparks in cardiomyocytes isolated from diabetic rats were also significantly altered to being almost parallel to the changes
of Ca 2+ transients. In addition, RyR2 from diabetic rat hearts were hyperphosphorylated and protein levels of both RyR2 and FKBP12.6
depleted. These data show that STZ-induced diabetic rat hearts exhibit altered local Ca 2+ signaling with increased basal Ca 2+ level.
RyR2, ryanodine receptor Ca release channel
SR, sarcoplasmic reticulum
STZ, streptozotocin
Footnotes
Accepted August 4, 2005.
Received May 11, 2005.
DIABETES |
| doi_str_mv | 10.2337/diabetes.54.11.3082 |
| format | Article |
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Nazmi Yaras 1 ,
Mehmet Ugur 1 ,
Semir Ozdemir 1 ,
Hakan Gurdal 2 ,
Nuhan Purali 3 ,
Alain Lacampagne 4 ,
Guy Vassort 4 and
Belma Turan 1
1 Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey
2 Department of Pharmacology, School of Medicine, Ankara University, Ankara, Turkey
3 Department of Biophysics, School of Medicine, Hacettepe University, Ankara, Turkey
4 INSERM U-637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, Montpellier, France
Address correspondence and reprint requests to Dr. Belma Turan, Department of Biophysics, School of Medicine, Ankara University,
Ankara, Turkey. E-mail: belma.turan{at}medicine.ankara.edu.tr
Abstract
The defects identified in the mechanical activity of the hearts from type 1 diabetic animals include alteration of Ca 2+ signaling via changes in critical processes that regulate intracellular Ca 2+ concentration. These defects result partially from a dysfunction of cardiac ryanodine receptor calcium release channel (RyR2).
The present study was designed to determine whether the properties of the Ca 2+ sparks might provide insight into the role of RyR2 in the altered Ca 2+ signaling in cardiomyocytes from diabetic animals when they were analyzed together with Ca 2+ transients. Basal Ca 2+ level as well as Ca 2+ -spark frequency of cardiomyoctes isolated from 5-week streptozotocin (STZ)-induced diabetic rats significantly increased
with respect to aged-matched control rats. Ca 2+ transients exhibited significantly reduced amplitude and prolonged time courses as well as depressed Ca 2+ loading of sarcoplasmic reticulum in diabetic rats. Spatio-temporal properties of the Ca 2+ sparks in cardiomyocytes isolated from diabetic rats were also significantly altered to being almost parallel to the changes
of Ca 2+ transients. In addition, RyR2 from diabetic rat hearts were hyperphosphorylated and protein levels of both RyR2 and FKBP12.6
depleted. These data show that STZ-induced diabetic rat hearts exhibit altered local Ca 2+ signaling with increased basal Ca 2+ level.
RyR2, ryanodine receptor Ca release channel
SR, sarcoplasmic reticulum
STZ, streptozotocin
Footnotes
Accepted August 4, 2005.
Received May 11, 2005.
DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/diabetes.54.11.3082</identifier><identifier>PMID: 16249429</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Animals ; Biological and medical sciences ; Caffeine - pharmacology ; Calcium - metabolism ; Calcium Signaling ; Diabetes Mellitus, Experimental - metabolism ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Gene Expression Regulation ; Heart - drug effects ; Homeostasis ; Insulin - pharmacology ; Medical sciences ; Myocardium - cytology ; Myocardium - metabolism ; Rats ; Ryanodine Receptor Calcium Release Channel - genetics ; Ryanodine Receptor Calcium Release Channel - metabolism ; Sarcoplasmic Reticulum - metabolism</subject><ispartof>Diabetes (New York, N.Y.), 2005-11, Vol.54 (11), p.3082-3088</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-30a29aabd1f7c971f59ed09f34aace80f5853cfd5eb50781698b114beabbbc1d3</citedby><cites>FETCH-LOGICAL-c411t-30a29aabd1f7c971f59ed09f34aace80f5853cfd5eb50781698b114beabbbc1d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17252829$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16249429$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>YARAS, Nazmi</creatorcontrib><creatorcontrib>UGUR, Mehmet</creatorcontrib><creatorcontrib>OZDEMIR, Semir</creatorcontrib><creatorcontrib>GURDAL, Hakan</creatorcontrib><creatorcontrib>PURALI, Nuhan</creatorcontrib><creatorcontrib>LACAMPAGNE, Alain</creatorcontrib><creatorcontrib>VASSORT, Guy</creatorcontrib><creatorcontrib>TURAN, Belma</creatorcontrib><title>Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca2+ Homeostasis in Rat Heart</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca 2+ Homeostasis in Rat Heart
Nazmi Yaras 1 ,
Mehmet Ugur 1 ,
Semir Ozdemir 1 ,
Hakan Gurdal 2 ,
Nuhan Purali 3 ,
Alain Lacampagne 4 ,
Guy Vassort 4 and
Belma Turan 1
1 Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey
2 Department of Pharmacology, School of Medicine, Ankara University, Ankara, Turkey
3 Department of Biophysics, School of Medicine, Hacettepe University, Ankara, Turkey
4 INSERM U-637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, Montpellier, France
Address correspondence and reprint requests to Dr. Belma Turan, Department of Biophysics, School of Medicine, Ankara University,
Ankara, Turkey. E-mail: belma.turan{at}medicine.ankara.edu.tr
Abstract
The defects identified in the mechanical activity of the hearts from type 1 diabetic animals include alteration of Ca 2+ signaling via changes in critical processes that regulate intracellular Ca 2+ concentration. These defects result partially from a dysfunction of cardiac ryanodine receptor calcium release channel (RyR2).
The present study was designed to determine whether the properties of the Ca 2+ sparks might provide insight into the role of RyR2 in the altered Ca 2+ signaling in cardiomyocytes from diabetic animals when they were analyzed together with Ca 2+ transients. Basal Ca 2+ level as well as Ca 2+ -spark frequency of cardiomyoctes isolated from 5-week streptozotocin (STZ)-induced diabetic rats significantly increased
with respect to aged-matched control rats. Ca 2+ transients exhibited significantly reduced amplitude and prolonged time courses as well as depressed Ca 2+ loading of sarcoplasmic reticulum in diabetic rats. Spatio-temporal properties of the Ca 2+ sparks in cardiomyocytes isolated from diabetic rats were also significantly altered to being almost parallel to the changes
of Ca 2+ transients. In addition, RyR2 from diabetic rat hearts were hyperphosphorylated and protein levels of both RyR2 and FKBP12.6
depleted. These data show that STZ-induced diabetic rat hearts exhibit altered local Ca 2+ signaling with increased basal Ca 2+ level.
RyR2, ryanodine receptor Ca release channel
SR, sarcoplasmic reticulum
STZ, streptozotocin
Footnotes
Accepted August 4, 2005.
Received May 11, 2005.
DIABETES</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Caffeine - pharmacology</subject><subject>Calcium - metabolism</subject><subject>Calcium Signaling</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Gene Expression Regulation</subject><subject>Heart - drug effects</subject><subject>Homeostasis</subject><subject>Insulin - pharmacology</subject><subject>Medical sciences</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Rats</subject><subject>Ryanodine Receptor Calcium Release Channel - genetics</subject><subject>Ryanodine Receptor Calcium Release Channel - metabolism</subject><subject>Sarcoplasmic Reticulum - metabolism</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkFGrEzEQhYMo3nr1FwiSF0XRrZlk02wepV6tcEEoCr6FSXZiV7ab3mSL9N-71670ReZhBuY758Bh7DmIpVTKvG879DRSWep6CbBUopEP2AKsspWS5sdDthACZAXGmiv2pJRfQojVNI_ZFaxkbWtpF4xuYqQwFp4i_zgb8jTw7QmH1HYD8S0FOowp8zVOd09YiK93OAzU89fb01a-4Ti001e-5Zu0p1RGLF3h3WSCI98Q5vEpexSxL_Rs3tfs-6ebb-tNdfv185f1h9sq1ABjpQRKi-hbiCZYA1FbaoWNqkYM1IioG61CbDV5LUwDK9t4gNoTeu8DtOqavTr7HnK6O1IZ3b4rgfoeB0rH4laNkcZqNYHqDIacSskU3SF3e8wnB8Ldt-v-tet07QDcfbuT6sVsf_R7ai-auc4JeDkDWAL2MeMQunLhjNSy-cu9O3O77ufud5fpEve_3D-arJOp</recordid><startdate>20051101</startdate><enddate>20051101</enddate><creator>YARAS, Nazmi</creator><creator>UGUR, Mehmet</creator><creator>OZDEMIR, Semir</creator><creator>GURDAL, Hakan</creator><creator>PURALI, Nuhan</creator><creator>LACAMPAGNE, Alain</creator><creator>VASSORT, Guy</creator><creator>TURAN, Belma</creator><general>American Diabetes Association</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20051101</creationdate><title>Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca2+ Homeostasis in Rat Heart</title><author>YARAS, Nazmi ; UGUR, Mehmet ; OZDEMIR, Semir ; GURDAL, Hakan ; PURALI, Nuhan ; LACAMPAGNE, Alain ; VASSORT, Guy ; TURAN, Belma</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-30a29aabd1f7c971f59ed09f34aace80f5853cfd5eb50781698b114beabbbc1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Caffeine - pharmacology</topic><topic>Calcium - metabolism</topic><topic>Calcium Signaling</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Gene Expression Regulation</topic><topic>Heart - drug effects</topic><topic>Homeostasis</topic><topic>Insulin - pharmacology</topic><topic>Medical sciences</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>Rats</topic><topic>Ryanodine Receptor Calcium Release Channel - genetics</topic><topic>Ryanodine Receptor Calcium Release Channel - metabolism</topic><topic>Sarcoplasmic Reticulum - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>YARAS, Nazmi</creatorcontrib><creatorcontrib>UGUR, Mehmet</creatorcontrib><creatorcontrib>OZDEMIR, Semir</creatorcontrib><creatorcontrib>GURDAL, Hakan</creatorcontrib><creatorcontrib>PURALI, Nuhan</creatorcontrib><creatorcontrib>LACAMPAGNE, Alain</creatorcontrib><creatorcontrib>VASSORT, Guy</creatorcontrib><creatorcontrib>TURAN, Belma</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>YARAS, Nazmi</au><au>UGUR, Mehmet</au><au>OZDEMIR, Semir</au><au>GURDAL, Hakan</au><au>PURALI, Nuhan</au><au>LACAMPAGNE, Alain</au><au>VASSORT, Guy</au><au>TURAN, Belma</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca2+ Homeostasis in Rat Heart</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2005-11-01</date><risdate>2005</risdate><volume>54</volume><issue>11</issue><spage>3082</spage><epage>3088</epage><pages>3082-3088</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca 2+ Homeostasis in Rat Heart
Nazmi Yaras 1 ,
Mehmet Ugur 1 ,
Semir Ozdemir 1 ,
Hakan Gurdal 2 ,
Nuhan Purali 3 ,
Alain Lacampagne 4 ,
Guy Vassort 4 and
Belma Turan 1
1 Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey
2 Department of Pharmacology, School of Medicine, Ankara University, Ankara, Turkey
3 Department of Biophysics, School of Medicine, Hacettepe University, Ankara, Turkey
4 INSERM U-637, Physiopathologie Cardiovasculaire, CHU Arnaud de Villeneuve, Montpellier, France
Address correspondence and reprint requests to Dr. Belma Turan, Department of Biophysics, School of Medicine, Ankara University,
Ankara, Turkey. E-mail: belma.turan{at}medicine.ankara.edu.tr
Abstract
The defects identified in the mechanical activity of the hearts from type 1 diabetic animals include alteration of Ca 2+ signaling via changes in critical processes that regulate intracellular Ca 2+ concentration. These defects result partially from a dysfunction of cardiac ryanodine receptor calcium release channel (RyR2).
The present study was designed to determine whether the properties of the Ca 2+ sparks might provide insight into the role of RyR2 in the altered Ca 2+ signaling in cardiomyocytes from diabetic animals when they were analyzed together with Ca 2+ transients. Basal Ca 2+ level as well as Ca 2+ -spark frequency of cardiomyoctes isolated from 5-week streptozotocin (STZ)-induced diabetic rats significantly increased
with respect to aged-matched control rats. Ca 2+ transients exhibited significantly reduced amplitude and prolonged time courses as well as depressed Ca 2+ loading of sarcoplasmic reticulum in diabetic rats. Spatio-temporal properties of the Ca 2+ sparks in cardiomyocytes isolated from diabetic rats were also significantly altered to being almost parallel to the changes
of Ca 2+ transients. In addition, RyR2 from diabetic rat hearts were hyperphosphorylated and protein levels of both RyR2 and FKBP12.6
depleted. These data show that STZ-induced diabetic rat hearts exhibit altered local Ca 2+ signaling with increased basal Ca 2+ level.
RyR2, ryanodine receptor Ca release channel
SR, sarcoplasmic reticulum
STZ, streptozotocin
Footnotes
Accepted August 4, 2005.
Received May 11, 2005.
DIABETES</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>16249429</pmid><doi>10.2337/diabetes.54.11.3082</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2005-11, Vol.54 (11), p.3082-3088 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_pubmed_primary_16249429 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Biological and medical sciences Caffeine - pharmacology Calcium - metabolism Calcium Signaling Diabetes Mellitus, Experimental - metabolism Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Gene Expression Regulation Heart - drug effects Homeostasis Insulin - pharmacology Medical sciences Myocardium - cytology Myocardium - metabolism Rats Ryanodine Receptor Calcium Release Channel - genetics Ryanodine Receptor Calcium Release Channel - metabolism Sarcoplasmic Reticulum - metabolism |
| title | Effects of Diabetes on Ryanodine Receptor Ca Release Channel (RyR2) and Ca2+ Homeostasis in Rat Heart |
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