Polysulfides are possible H2S‐derived signaling molecules in rat brain
Accumulating evidence shows that hydrogen sulfide (H2S) has a variety of physiological functions. H2S is produced from cysteine by 3 sulfurtransferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca2+ influx in astrocytes, a type of glia. Howeve...
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| Veröffentlicht in: | The FASEB journal 2013-06, Vol.27 (6), p.2451-2457 |
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| creator | Kimura, Yuka Mikami, Yoshinori Osumi, Kimiko Tsugane, Mamiko Oka, Jun‐ichiro Kimura, Hideo |
| description | Accumulating evidence shows that hydrogen sulfide (H2S) has a variety of physiological functions. H2S is produced from cysteine by 3 sulfurtransferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca2+ influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca2+ influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes (EC50 91 nM, Hill coefficient value 1.77±0.26) and that the maximum response was induced at 0.5 μM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 μM, EC50 116 μM). TRPA1‐selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca2+ influx, and responses to polysulfides were suppressed by TRPA1‐selective inhibitors, HC‐030031 and AP‐18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H2S‐derived signaling molecules that stimulate TRP channels in the brain.—Kimura, Y., Mikami, Y., Osumi, K., Tsugane, M., Oka, J., Kimura, H. Polysulfides are possible H2S‐derived signaling molecules in rat brain. FASEB J. 27, 2451–2457 (2013). www.fasebj.org |
| doi_str_mv | 10.1096/fj.12-226415 |
| format | Article |
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H2S is produced from cysteine by 3 sulfurtransferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca2+ influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca2+ influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes (EC50 91 nM, Hill coefficient value 1.77±0.26) and that the maximum response was induced at 0.5 μM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 μM, EC50 116 μM). TRPA1‐selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca2+ influx, and responses to polysulfides were suppressed by TRPA1‐selective inhibitors, HC‐030031 and AP‐18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H2S‐derived signaling molecules that stimulate TRP channels in the brain.—Kimura, Y., Mikami, Y., Osumi, K., Tsugane, M., Oka, J., Kimura, H. Polysulfides are possible H2S‐derived signaling molecules in rat brain. FASEB J. 27, 2451–2457 (2013). www.fasebj.org</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.12-226415</identifier><identifier>PMID: 23413359</identifier><language>eng</language><publisher>Bethesda, MD, USA: Federation of American Societies for Experimental Biology</publisher><subject>Acetanilides - pharmacology ; Acrolein - analogs & derivatives ; Acrolein - pharmacology ; Animals ; Astrocytes - drug effects ; Astrocytes - metabolism ; Brain - metabolism ; Ca2+ influx ; Calcium Signaling - drug effects ; Gadolinium - pharmacology ; hydrogen sulfide ; Hydrogen Sulfide - metabolism ; Isothiocyanates - pharmacology ; Lanthanum - pharmacology ; Male ; Mice ; persulfide ; Purines - pharmacology ; Rats ; Rats, Sprague-Dawley ; RNA, Small Interfering - genetics ; Ruthenium Red - pharmacology ; Signal Transduction ; Sulfides - metabolism ; TRP channels ; TRPA1 Cation Channel ; TRPC Cation Channels - agonists ; TRPC Cation Channels - antagonists & inhibitors ; TRPC Cation Channels - metabolism</subject><ispartof>The FASEB journal, 2013-06, Vol.27 (6), p.2451-2457</ispartof><rights>FASEB</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.12-226415$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.12-226415$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23413359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kimura, Yuka</creatorcontrib><creatorcontrib>Mikami, Yoshinori</creatorcontrib><creatorcontrib>Osumi, Kimiko</creatorcontrib><creatorcontrib>Tsugane, Mamiko</creatorcontrib><creatorcontrib>Oka, Jun‐ichiro</creatorcontrib><creatorcontrib>Kimura, Hideo</creatorcontrib><title>Polysulfides are possible H2S‐derived signaling molecules in rat brain</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>Accumulating evidence shows that hydrogen sulfide (H2S) has a variety of physiological functions. H2S is produced from cysteine by 3 sulfurtransferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca2+ influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca2+ influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes (EC50 91 nM, Hill coefficient value 1.77±0.26) and that the maximum response was induced at 0.5 μM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 μM, EC50 116 μM). TRPA1‐selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca2+ influx, and responses to polysulfides were suppressed by TRPA1‐selective inhibitors, HC‐030031 and AP‐18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H2S‐derived signaling molecules that stimulate TRP channels in the brain.—Kimura, Y., Mikami, Y., Osumi, K., Tsugane, M., Oka, J., Kimura, H. Polysulfides are possible H2S‐derived signaling molecules in rat brain. FASEB J. 27, 2451–2457 (2013). www.fasebj.org</description><subject>Acetanilides - pharmacology</subject><subject>Acrolein - analogs & derivatives</subject><subject>Acrolein - pharmacology</subject><subject>Animals</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Brain - metabolism</subject><subject>Ca2+ influx</subject><subject>Calcium Signaling - drug effects</subject><subject>Gadolinium - pharmacology</subject><subject>hydrogen sulfide</subject><subject>Hydrogen Sulfide - metabolism</subject><subject>Isothiocyanates - pharmacology</subject><subject>Lanthanum - pharmacology</subject><subject>Male</subject><subject>Mice</subject><subject>persulfide</subject><subject>Purines - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Small Interfering - genetics</subject><subject>Ruthenium Red - pharmacology</subject><subject>Signal Transduction</subject><subject>Sulfides - metabolism</subject><subject>TRP channels</subject><subject>TRPA1 Cation Channel</subject><subject>TRPC Cation Channels - agonists</subject><subject>TRPC Cation Channels - antagonists & inhibitors</subject><subject>TRPC Cation Channels - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo90L9OwzAQBnALgWgpbMzII0vK2U6ceISKUqRKIBVmy46dypXzB7sBdeMReEaehKAWphvup0_fHUKXBKYEBL-pNlNCE0p5SrIjNCYZg4QXHI7RGApBE85ZMUJnMW4AgADhp2hEWUoYy8QYLZ5bv4u9r5yxEatgcdfG6LS3eEFX359fxgb3bg2Obt0o75o1rltvy94P3DU4qC3WQbnmHJ1Uykd7cZgT9Dq_f5ktkuXTw-Psdpl0pBAsKXOtNQWjLM3yNAOoTMEEBTAigxyIplSoYqhXCqEqC2ooLUoQwmgzeMIm6Hqf24X2rbdxK2sXS-u9amzbR0k4hxSAp8VArw6017U1sguuVmEn_64fQL4HH87b3f-egPz9rKw2klC5_6ycr-4o0HxIBsbYD-IYa1o</recordid><startdate>201306</startdate><enddate>201306</enddate><creator>Kimura, Yuka</creator><creator>Mikami, Yoshinori</creator><creator>Osumi, Kimiko</creator><creator>Tsugane, Mamiko</creator><creator>Oka, Jun‐ichiro</creator><creator>Kimura, Hideo</creator><general>Federation of American Societies for Experimental Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>201306</creationdate><title>Polysulfides are possible H2S‐derived signaling molecules in rat brain</title><author>Kimura, Yuka ; Mikami, Yoshinori ; Osumi, Kimiko ; Tsugane, Mamiko ; Oka, Jun‐ichiro ; Kimura, Hideo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p1893-c7bbb20dae2574500fd839200d950701b229a8341c99afe0a0009c099dbd74513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetanilides - pharmacology</topic><topic>Acrolein - analogs & derivatives</topic><topic>Acrolein - pharmacology</topic><topic>Animals</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Brain - metabolism</topic><topic>Ca2+ influx</topic><topic>Calcium Signaling - drug effects</topic><topic>Gadolinium - pharmacology</topic><topic>hydrogen sulfide</topic><topic>Hydrogen Sulfide - metabolism</topic><topic>Isothiocyanates - pharmacology</topic><topic>Lanthanum - pharmacology</topic><topic>Male</topic><topic>Mice</topic><topic>persulfide</topic><topic>Purines - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Small Interfering - genetics</topic><topic>Ruthenium Red - pharmacology</topic><topic>Signal Transduction</topic><topic>Sulfides - metabolism</topic><topic>TRP channels</topic><topic>TRPA1 Cation Channel</topic><topic>TRPC Cation Channels - agonists</topic><topic>TRPC Cation Channels - antagonists & inhibitors</topic><topic>TRPC Cation Channels - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kimura, Yuka</creatorcontrib><creatorcontrib>Mikami, Yoshinori</creatorcontrib><creatorcontrib>Osumi, Kimiko</creatorcontrib><creatorcontrib>Tsugane, Mamiko</creatorcontrib><creatorcontrib>Oka, Jun‐ichiro</creatorcontrib><creatorcontrib>Kimura, Hideo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kimura, Yuka</au><au>Mikami, Yoshinori</au><au>Osumi, Kimiko</au><au>Tsugane, Mamiko</au><au>Oka, Jun‐ichiro</au><au>Kimura, Hideo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polysulfides are possible H2S‐derived signaling molecules in rat brain</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2013-06</date><risdate>2013</risdate><volume>27</volume><issue>6</issue><spage>2451</spage><epage>2457</epage><pages>2451-2457</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Accumulating evidence shows that hydrogen sulfide (H2S) has a variety of physiological functions. H2S is produced from cysteine by 3 sulfurtransferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca2+ influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca2+ influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes (EC50 91 nM, Hill coefficient value 1.77±0.26) and that the maximum response was induced at 0.5 μM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 μM, EC50 116 μM). TRPA1‐selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca2+ influx, and responses to polysulfides were suppressed by TRPA1‐selective inhibitors, HC‐030031 and AP‐18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H2S‐derived signaling molecules that stimulate TRP channels in the brain.—Kimura, Y., Mikami, Y., Osumi, K., Tsugane, M., Oka, J., Kimura, H. Polysulfides are possible H2S‐derived signaling molecules in rat brain. FASEB J. 27, 2451–2457 (2013). www.fasebj.org</abstract><cop>Bethesda, MD, USA</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>23413359</pmid><doi>10.1096/fj.12-226415</doi><tpages>7</tpages></addata></record> |
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| subjects | Acetanilides - pharmacology Acrolein - analogs & derivatives Acrolein - pharmacology Animals Astrocytes - drug effects Astrocytes - metabolism Brain - metabolism Ca2+ influx Calcium Signaling - drug effects Gadolinium - pharmacology hydrogen sulfide Hydrogen Sulfide - metabolism Isothiocyanates - pharmacology Lanthanum - pharmacology Male Mice persulfide Purines - pharmacology Rats Rats, Sprague-Dawley RNA, Small Interfering - genetics Ruthenium Red - pharmacology Signal Transduction Sulfides - metabolism TRP channels TRPA1 Cation Channel TRPC Cation Channels - agonists TRPC Cation Channels - antagonists & inhibitors TRPC Cation Channels - metabolism |
| title | Polysulfides are possible H2S‐derived signaling molecules in rat brain |
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