The effects of sphingosine on sarcoplasmic reticulum membrane calcium release
In this study, we report that sphingosine is a potent inhibitor of sarcoplasmic reticulum (SR) calcium release. Evidence is presented demonstrating a direct effect of sphingosine on the SR ryanodine receptor. Calcium release from "skinned" rabbit skeletal muscle fibers and isolated junctio...
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| Veröffentlicht in: | The Journal of biological chemistry 1992-08, Vol.267 (22), p.15475-15484 |
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| creator | SABBADINI, R. A BETTO, R TERESI, A FACHECHI-CASSANO, G SALVIATI, G |
| description | In this study, we report that sphingosine is a potent inhibitor of sarcoplasmic reticulum (SR) calcium release. Evidence is
presented demonstrating a direct effect of sphingosine on the SR ryanodine receptor. Calcium release from "skinned" rabbit
skeletal muscle fibers and isolated junctional SR derived from the terminal cisternae (TC) was measured in response to caffeine,
doxorubicin, 5'-adenylyl-beta,gamma-imidodiphosphate or calcium. Sphingosine inhibited caffeine-induced release in a dose-dependent
manner with an IC50 of 0.1 microM for the single muscle fibers and 0.5 microM for the isolated TC vesicles. Near complete
blockage of TC calcium release rate was observed with 3 microM sphingosine. Neither sphingomyelin nor sphingosylphosphorylcholine
had any effect at the 3 microM level, suggesting that the sphingosine effect was specific. Doxorubicin-induced calcium release
and spontaneous calcium release were also blocked by sphingosine. Sphingosine was also capable of stimulating calcium transport
in the isolated TC vesicles without an effect on Ca-ATPase activity. Ruthenium red was not capable of substantial additional
stimulation of calcium transport nor inhibition of calcium release beyond the action of sphingosine. Sphingosine's blockage
of calcium release was not reversed by the protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2- methylpiperazine dihydrochloride,
suggesting that the action of sphingosine on calcium release was not dependent on ryanodine receptor phosphorylation. Sphingosine
significantly increased (8-fold) the Kd for specific [3H]ryanodine binding to TC membranes and decreased the Bmax with a dose
dependence similar to the inhibition of calcium release, but sphingosine did not affect the pCa tension relationship of skinned
skeletal muscle fibers. These data are consistent with a direct effect of submicromolar sphingosine on the ryanodine receptor.
Substantially higher concentrations of sphingosine (30-50 microM) or sphingosylphosphorylcholine (10-20 microM) were capable
of inducing calcium release by themselves. Preliminary data indicate that the transverse tubule and not the SR contain substantial
sphingomyelinase activity consistent with a transverse tubule source of sphingosine production. Considering that sphingosine
is found in micromolar concentrations in some cells, our data indicate that sphingosine generated by the transverse tubule
membranes may be a physiologically relevant mechanism for modulating SR calcium release. |
| doi_str_mv | 10.1016/S0021-9258(19)49559-8 |
| format | Article |
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presented demonstrating a direct effect of sphingosine on the SR ryanodine receptor. Calcium release from "skinned" rabbit
skeletal muscle fibers and isolated junctional SR derived from the terminal cisternae (TC) was measured in response to caffeine,
doxorubicin, 5'-adenylyl-beta,gamma-imidodiphosphate or calcium. Sphingosine inhibited caffeine-induced release in a dose-dependent
manner with an IC50 of 0.1 microM for the single muscle fibers and 0.5 microM for the isolated TC vesicles. Near complete
blockage of TC calcium release rate was observed with 3 microM sphingosine. Neither sphingomyelin nor sphingosylphosphorylcholine
had any effect at the 3 microM level, suggesting that the sphingosine effect was specific. Doxorubicin-induced calcium release
and spontaneous calcium release were also blocked by sphingosine. Sphingosine was also capable of stimulating calcium transport
in the isolated TC vesicles without an effect on Ca-ATPase activity. Ruthenium red was not capable of substantial additional
stimulation of calcium transport nor inhibition of calcium release beyond the action of sphingosine. Sphingosine's blockage
of calcium release was not reversed by the protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2- methylpiperazine dihydrochloride,
suggesting that the action of sphingosine on calcium release was not dependent on ryanodine receptor phosphorylation. Sphingosine
significantly increased (8-fold) the Kd for specific [3H]ryanodine binding to TC membranes and decreased the Bmax with a dose
dependence similar to the inhibition of calcium release, but sphingosine did not affect the pCa tension relationship of skinned
skeletal muscle fibers. These data are consistent with a direct effect of submicromolar sphingosine on the ryanodine receptor.
Substantially higher concentrations of sphingosine (30-50 microM) or sphingosylphosphorylcholine (10-20 microM) were capable
of inducing calcium release by themselves. Preliminary data indicate that the transverse tubule and not the SR contain substantial
sphingomyelinase activity consistent with a transverse tubule source of sphingosine production. Considering that sphingosine
is found in micromolar concentrations in some cells, our data indicate that sphingosine generated by the transverse tubule
membranes may be a physiologically relevant mechanism for modulating SR calcium release.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(19)49559-8</identifier><identifier>PMID: 1386359</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Biochemistry and Molecular Biology</publisher><subject>Animals ; Biological and medical sciences ; Caffeine - pharmacology ; calcium ; Calcium - metabolism ; Calcium-Transporting ATPases - metabolism ; Cell physiology ; Doxorubicin - pharmacology ; effects on ; Fundamental and applied biological sciences. Psychology ; Kinetics ; Membrane and intracellular transports ; Molecular and cellular biology ; Muscles - metabolism ; Rabbits ; release ; Ryanodine - metabolism ; sarcoplasmic reticulum ; Sarcoplasmic Reticulum - drug effects ; Sarcoplasmic Reticulum - metabolism ; skeletal muscle ; Sphingomyelin Phosphodiesterase - metabolism ; Sphingomyelins - pharmacology ; sphingosine ; Sphingosine - pharmacology</subject><ispartof>The Journal of biological chemistry, 1992-08, Vol.267 (22), p.15475-15484</ispartof><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-7332cea325f77b908169d29d2fb149b3379b38f18eefb42cd5a336be25f462793</citedby><cites>FETCH-LOGICAL-c440t-7332cea325f77b908169d29d2fb149b3379b38f18eefb42cd5a336be25f462793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5506779$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1386359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SABBADINI, R. A</creatorcontrib><creatorcontrib>BETTO, R</creatorcontrib><creatorcontrib>TERESI, A</creatorcontrib><creatorcontrib>FACHECHI-CASSANO, G</creatorcontrib><creatorcontrib>SALVIATI, G</creatorcontrib><title>The effects of sphingosine on sarcoplasmic reticulum membrane calcium release</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>In this study, we report that sphingosine is a potent inhibitor of sarcoplasmic reticulum (SR) calcium release. Evidence is
presented demonstrating a direct effect of sphingosine on the SR ryanodine receptor. Calcium release from "skinned" rabbit
skeletal muscle fibers and isolated junctional SR derived from the terminal cisternae (TC) was measured in response to caffeine,
doxorubicin, 5'-adenylyl-beta,gamma-imidodiphosphate or calcium. Sphingosine inhibited caffeine-induced release in a dose-dependent
manner with an IC50 of 0.1 microM for the single muscle fibers and 0.5 microM for the isolated TC vesicles. Near complete
blockage of TC calcium release rate was observed with 3 microM sphingosine. Neither sphingomyelin nor sphingosylphosphorylcholine
had any effect at the 3 microM level, suggesting that the sphingosine effect was specific. Doxorubicin-induced calcium release
and spontaneous calcium release were also blocked by sphingosine. Sphingosine was also capable of stimulating calcium transport
in the isolated TC vesicles without an effect on Ca-ATPase activity. Ruthenium red was not capable of substantial additional
stimulation of calcium transport nor inhibition of calcium release beyond the action of sphingosine. Sphingosine's blockage
of calcium release was not reversed by the protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2- methylpiperazine dihydrochloride,
suggesting that the action of sphingosine on calcium release was not dependent on ryanodine receptor phosphorylation. Sphingosine
significantly increased (8-fold) the Kd for specific [3H]ryanodine binding to TC membranes and decreased the Bmax with a dose
dependence similar to the inhibition of calcium release, but sphingosine did not affect the pCa tension relationship of skinned
skeletal muscle fibers. These data are consistent with a direct effect of submicromolar sphingosine on the ryanodine receptor.
Substantially higher concentrations of sphingosine (30-50 microM) or sphingosylphosphorylcholine (10-20 microM) were capable
of inducing calcium release by themselves. Preliminary data indicate that the transverse tubule and not the SR contain substantial
sphingomyelinase activity consistent with a transverse tubule source of sphingosine production. Considering that sphingosine
is found in micromolar concentrations in some cells, our data indicate that sphingosine generated by the transverse tubule
membranes may be a physiologically relevant mechanism for modulating SR calcium release.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Caffeine - pharmacology</subject><subject>calcium</subject><subject>Calcium - metabolism</subject><subject>Calcium-Transporting ATPases - metabolism</subject><subject>Cell physiology</subject><subject>Doxorubicin - pharmacology</subject><subject>effects on</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Kinetics</subject><subject>Membrane and intracellular transports</subject><subject>Molecular and cellular biology</subject><subject>Muscles - metabolism</subject><subject>Rabbits</subject><subject>release</subject><subject>Ryanodine - metabolism</subject><subject>sarcoplasmic reticulum</subject><subject>Sarcoplasmic Reticulum - drug effects</subject><subject>Sarcoplasmic Reticulum - metabolism</subject><subject>skeletal muscle</subject><subject>Sphingomyelin Phosphodiesterase - metabolism</subject><subject>Sphingomyelins - pharmacology</subject><subject>sphingosine</subject><subject>Sphingosine - pharmacology</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtrGzEQgEVJSNy0P8GwhxDawyYaPVfHEtqm4NBDE-hNaOWRV2HX60heSv59lNg4vUUIDWi-efARMgd6CRTU1R9KGdSGyeYLmK_CSGnq5gOZAW14zSX8PSKzA3JKPub8QMsRBk7ICfBGcWlm5PauwwpDQL_N1RiqvOniejXmuMZqXFfZJT9uepeH6KuE2-infhqqAYc2uYJ41_tYPhL26DJ-IsfB9Rk_7-MZuf_x_e76pl78_vnr-tui9kLQba05Zx4dZzJo3RragDJLVm5oQZiWc12eJkCDGFrB_FI6zlWLhReKacPPyMWu7yaNjxPmrR1i9tj3ZadxylZzarjU9F0QFGcGlCig3IE-jTknDHaT4uDSkwVqX3zbV9_2RaYFY19926bUzfcDpnbA5VvVTnDJn-_zLhdZoVjzMR8wKanS-j-si6vuX0xo2zj6DgfLlLaMWZBCS_4M6g2Tvw</recordid><startdate>19920805</startdate><enddate>19920805</enddate><creator>SABBADINI, R. A</creator><creator>BETTO, R</creator><creator>TERESI, A</creator><creator>FACHECHI-CASSANO, G</creator><creator>SALVIATI, G</creator><general>American Society for Biochemistry and Molecular Biology</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>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19920805</creationdate><title>The effects of sphingosine on sarcoplasmic reticulum membrane calcium release</title><author>SABBADINI, R. A ; BETTO, R ; TERESI, A ; FACHECHI-CASSANO, G ; SALVIATI, G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-7332cea325f77b908169d29d2fb149b3379b38f18eefb42cd5a336be25f462793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Caffeine - pharmacology</topic><topic>calcium</topic><topic>Calcium - metabolism</topic><topic>Calcium-Transporting ATPases - metabolism</topic><topic>Cell physiology</topic><topic>Doxorubicin - pharmacology</topic><topic>effects on</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Kinetics</topic><topic>Membrane and intracellular transports</topic><topic>Molecular and cellular biology</topic><topic>Muscles - metabolism</topic><topic>Rabbits</topic><topic>release</topic><topic>Ryanodine - metabolism</topic><topic>sarcoplasmic reticulum</topic><topic>Sarcoplasmic Reticulum - drug effects</topic><topic>Sarcoplasmic Reticulum - metabolism</topic><topic>skeletal muscle</topic><topic>Sphingomyelin Phosphodiesterase - metabolism</topic><topic>Sphingomyelins - pharmacology</topic><topic>sphingosine</topic><topic>Sphingosine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SABBADINI, R. A</creatorcontrib><creatorcontrib>BETTO, R</creatorcontrib><creatorcontrib>TERESI, A</creatorcontrib><creatorcontrib>FACHECHI-CASSANO, G</creatorcontrib><creatorcontrib>SALVIATI, G</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SABBADINI, R. A</au><au>BETTO, R</au><au>TERESI, A</au><au>FACHECHI-CASSANO, G</au><au>SALVIATI, G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effects of sphingosine on sarcoplasmic reticulum membrane calcium release</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1992-08-05</date><risdate>1992</risdate><volume>267</volume><issue>22</issue><spage>15475</spage><epage>15484</epage><pages>15475-15484</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>In this study, we report that sphingosine is a potent inhibitor of sarcoplasmic reticulum (SR) calcium release. Evidence is
presented demonstrating a direct effect of sphingosine on the SR ryanodine receptor. Calcium release from "skinned" rabbit
skeletal muscle fibers and isolated junctional SR derived from the terminal cisternae (TC) was measured in response to caffeine,
doxorubicin, 5'-adenylyl-beta,gamma-imidodiphosphate or calcium. Sphingosine inhibited caffeine-induced release in a dose-dependent
manner with an IC50 of 0.1 microM for the single muscle fibers and 0.5 microM for the isolated TC vesicles. Near complete
blockage of TC calcium release rate was observed with 3 microM sphingosine. Neither sphingomyelin nor sphingosylphosphorylcholine
had any effect at the 3 microM level, suggesting that the sphingosine effect was specific. Doxorubicin-induced calcium release
and spontaneous calcium release were also blocked by sphingosine. Sphingosine was also capable of stimulating calcium transport
in the isolated TC vesicles without an effect on Ca-ATPase activity. Ruthenium red was not capable of substantial additional
stimulation of calcium transport nor inhibition of calcium release beyond the action of sphingosine. Sphingosine's blockage
of calcium release was not reversed by the protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2- methylpiperazine dihydrochloride,
suggesting that the action of sphingosine on calcium release was not dependent on ryanodine receptor phosphorylation. Sphingosine
significantly increased (8-fold) the Kd for specific [3H]ryanodine binding to TC membranes and decreased the Bmax with a dose
dependence similar to the inhibition of calcium release, but sphingosine did not affect the pCa tension relationship of skinned
skeletal muscle fibers. These data are consistent with a direct effect of submicromolar sphingosine on the ryanodine receptor.
Substantially higher concentrations of sphingosine (30-50 microM) or sphingosylphosphorylcholine (10-20 microM) were capable
of inducing calcium release by themselves. Preliminary data indicate that the transverse tubule and not the SR contain substantial
sphingomyelinase activity consistent with a transverse tubule source of sphingosine production. Considering that sphingosine
is found in micromolar concentrations in some cells, our data indicate that sphingosine generated by the transverse tubule
membranes may be a physiologically relevant mechanism for modulating SR calcium release.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>1386359</pmid><doi>10.1016/S0021-9258(19)49559-8</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | The Journal of biological chemistry, 1992-08, Vol.267 (22), p.15475-15484 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73093570 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Biological and medical sciences Caffeine - pharmacology calcium Calcium - metabolism Calcium-Transporting ATPases - metabolism Cell physiology Doxorubicin - pharmacology effects on Fundamental and applied biological sciences. Psychology Kinetics Membrane and intracellular transports Molecular and cellular biology Muscles - metabolism Rabbits release Ryanodine - metabolism sarcoplasmic reticulum Sarcoplasmic Reticulum - drug effects Sarcoplasmic Reticulum - metabolism skeletal muscle Sphingomyelin Phosphodiesterase - metabolism Sphingomyelins - pharmacology sphingosine Sphingosine - pharmacology |
| title | The effects of sphingosine on sarcoplasmic reticulum membrane calcium release |
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