Ca2+ Depletion in the ER Causes Store-Operated Ca2+ Entry via the TRPC6 Channel in Mouse Brown Adipocytes
beta3-adrenergic activation causes Ca2+ release from the mitochondria and subsequent Ca2+ release from the endoplasmic reticulum (ER), evoking store-operated Ca2+ entry (SOCE) due to Ca2+ depletion from the ER in mouse brown adipocytes. In this study, we investigated how Ca2+ depletion from the ER e...
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| Veröffentlicht in: | Physiological research 2024-03, Vol.73 (1), p.69-80 |
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| description | beta3-adrenergic activation causes Ca2+ release from the mitochondria and subsequent Ca2+ release from the endoplasmic reticulum (ER), evoking store-operated Ca2+ entry (SOCE) due to Ca2+ depletion from the ER in mouse brown adipocytes. In this study, we investigated how Ca2+ depletion from the ER elicits SOCE in mouse brown adipocytes using fluorometry of intracellular Ca2+ concentration ([Ca2+]i). The administration of cyclopiazonic acid (CPA), a reversible sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump blocker in the ER, caused an increase in [Ca2+]i. Moreover, CPA induced SOCE was suppressed by the administration of a Ca2+ free Krebs solution and the transient receptor potential canonical 6 (TRPC6) selective blockers 2-APB, ML-9 and GsMTx-4 but not Pico145, which blocks TRPC1/4/5. Administration of TRPC6 channel agonist 1-oleoyl-2-acetyl-sn-glycerol (OAG) and flufenamic acid elicited Ca2+ entry. Moreover, our RT-PCR analyses detected mRNAs for TRPC6 in brown adipose tissues. In addition, western blot analyses showed the expression of the TRPC6 protein. Thus, TRPC6 is one of the Ca2+ pathways involved in SOCE. These modes of Ca2+ entry provide the basis for heat production via activation of Ca2+-dependent dehydrogenase and the expression of uncoupling protein 1 (UCP1). Enhancing thermogenic metabolism in brown adipocytes may serve as broad therapeutic utility to reduce obesity and metabolic syndrome. |
| doi_str_mv | 10.33549/physiolres.935071 |
| format | Article |
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In this study, we investigated how Ca2+ depletion from the ER elicits SOCE in mouse brown adipocytes using fluorometry of intracellular Ca2+ concentration ([Ca2+]i). The administration of cyclopiazonic acid (CPA), a reversible sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump blocker in the ER, caused an increase in [Ca2+]i. Moreover, CPA induced SOCE was suppressed by the administration of a Ca2+ free Krebs solution and the transient receptor potential canonical 6 (TRPC6) selective blockers 2-APB, ML-9 and GsMTx-4 but not Pico145, which blocks TRPC1/4/5. Administration of TRPC6 channel agonist 1-oleoyl-2-acetyl-sn-glycerol (OAG) and flufenamic acid elicited Ca2+ entry. Moreover, our RT-PCR analyses detected mRNAs for TRPC6 in brown adipose tissues. In addition, western blot analyses showed the expression of the TRPC6 protein. Thus, TRPC6 is one of the Ca2+ pathways involved in SOCE. These modes of Ca2+ entry provide the basis for heat production via activation of Ca2+-dependent dehydrogenase and the expression of uncoupling protein 1 (UCP1). Enhancing thermogenic metabolism in brown adipocytes may serve as broad therapeutic utility to reduce obesity and metabolic syndrome.</description><identifier>ISSN: 0862-8408</identifier><identifier>EISSN: 1802-9973</identifier><identifier>DOI: 10.33549/physiolres.935071</identifier><identifier>PMID: 38466006</identifier><language>eng</language><publisher>Czech Republic: Institute of Physiology</publisher><subject>Adipocytes ; Adipocytes, Brown - metabolism ; Adipose tissue ; Adrenergic receptors ; Animals ; Ca2+-transporting ATPase ; Calcium (intracellular) ; Calcium (reticular) ; Calcium - metabolism ; Calcium influx ; Calcium Signaling ; Cyclopiazonic acid ; Dehydrogenases ; Endoplasmic reticulum ; Endoplasmic Reticulum - metabolism ; Fluorometry ; Homeostasis ; Kinases ; Metabolic syndrome ; Mice ; Mitochondria ; Photonics ; Physiology ; Protein turnover ; Proteins ; Thermogenesis ; Transient Receptor Potential Channels - metabolism ; Transient receptor potential proteins ; Triglycerides ; TRPC Cation Channels - metabolism ; TRPC6 Cation Channel - metabolism ; Uncoupling protein 1</subject><ispartof>Physiological research, 2024-03, Vol.73 (1), p.69-80</ispartof><rights>Copyright Institute of Physiology 2024</rights><rights>2024 Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c279t-e40cc96d4595cc9a8aeb4fa3b0d148d70e1d9b0d71ea13e95adfee1f981afcf93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019620/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019620/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38466006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hayato, R</creatorcontrib><creatorcontrib>Matsumoto, T</creatorcontrib><creatorcontrib>Higure, Y</creatorcontrib><title>Ca2+ Depletion in the ER Causes Store-Operated Ca2+ Entry via the TRPC6 Channel in Mouse Brown Adipocytes</title><title>Physiological research</title><addtitle>Physiol Res</addtitle><description>beta3-adrenergic activation causes Ca2+ release from the mitochondria and subsequent Ca2+ release from the endoplasmic reticulum (ER), evoking store-operated Ca2+ entry (SOCE) due to Ca2+ depletion from the ER in mouse brown adipocytes. In this study, we investigated how Ca2+ depletion from the ER elicits SOCE in mouse brown adipocytes using fluorometry of intracellular Ca2+ concentration ([Ca2+]i). The administration of cyclopiazonic acid (CPA), a reversible sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump blocker in the ER, caused an increase in [Ca2+]i. Moreover, CPA induced SOCE was suppressed by the administration of a Ca2+ free Krebs solution and the transient receptor potential canonical 6 (TRPC6) selective blockers 2-APB, ML-9 and GsMTx-4 but not Pico145, which blocks TRPC1/4/5. Administration of TRPC6 channel agonist 1-oleoyl-2-acetyl-sn-glycerol (OAG) and flufenamic acid elicited Ca2+ entry. Moreover, our RT-PCR analyses detected mRNAs for TRPC6 in brown adipose tissues. In addition, western blot analyses showed the expression of the TRPC6 protein. Thus, TRPC6 is one of the Ca2+ pathways involved in SOCE. These modes of Ca2+ entry provide the basis for heat production via activation of Ca2+-dependent dehydrogenase and the expression of uncoupling protein 1 (UCP1). Enhancing thermogenic metabolism in brown adipocytes may serve as broad therapeutic utility to reduce obesity and metabolic syndrome.</description><subject>Adipocytes</subject><subject>Adipocytes, Brown - metabolism</subject><subject>Adipose tissue</subject><subject>Adrenergic receptors</subject><subject>Animals</subject><subject>Ca2+-transporting ATPase</subject><subject>Calcium (intracellular)</subject><subject>Calcium (reticular)</subject><subject>Calcium - metabolism</subject><subject>Calcium influx</subject><subject>Calcium Signaling</subject><subject>Cyclopiazonic acid</subject><subject>Dehydrogenases</subject><subject>Endoplasmic reticulum</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>Fluorometry</subject><subject>Homeostasis</subject><subject>Kinases</subject><subject>Metabolic syndrome</subject><subject>Mice</subject><subject>Mitochondria</subject><subject>Photonics</subject><subject>Physiology</subject><subject>Protein turnover</subject><subject>Proteins</subject><subject>Thermogenesis</subject><subject>Transient Receptor Potential Channels - metabolism</subject><subject>Transient receptor potential proteins</subject><subject>Triglycerides</subject><subject>TRPC Cation Channels - metabolism</subject><subject>TRPC6 Cation Channel - metabolism</subject><subject>Uncoupling protein 1</subject><issn>0862-8408</issn><issn>1802-9973</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpVUclOwzAQtRAIyvIDHJAljigwjpPYPiEIZZFARSxny00m1CjEwU6L-veEtmynmdG8TXqE7DM45jxN1Ek7mQfrao_hWPEUBFsjAyYhjpQSfJ0MQGZxJBOQW2Q7hFeAWIDgm2SLyyTLALIBsbmJj-gFtjV21jXUNrSbIB0-0NxMAwb62DmP0ahFbzos6QI-bDo_pzNrFtinh_s8o_nENA3WXwJ3rmfSc-8-GnpW2tYV8w7DLtmoTB1wbzV3yPPl8Cm_jm5HVzf52W1UxEJ1ESZQFCork1Sl_WKkwXFSGT6GkiWyFICsVP0hGBrGUaWmrBBZpSQzVVEpvkNOl7rtdPyGZYF9WFPr1ts34-faGav_fxo70S9uphkDprIYeoXDlYJ371MMnX51U9_0oTUHloIUTHz5xEtU4V0IHqsfCwZ60Y_-7Ucv--lJB3_D_VC-C-Gf6e2Pkg</recordid><startdate>20240311</startdate><enddate>20240311</enddate><creator>Hayato, R</creator><creator>Matsumoto, T</creator><creator>Higure, Y</creator><general>Institute of Physiology</general><general>Institute of Physiology of the Czech Academy of Sciences</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>4T-</scope><scope>4U-</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BYOGL</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20240311</creationdate><title>Ca2+ Depletion in the ER Causes Store-Operated Ca2+ Entry via the TRPC6 Channel in Mouse Brown Adipocytes</title><author>Hayato, R ; Matsumoto, T ; Higure, Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c279t-e40cc96d4595cc9a8aeb4fa3b0d148d70e1d9b0d71ea13e95adfee1f981afcf93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adipocytes</topic><topic>Adipocytes, Brown - metabolism</topic><topic>Adipose tissue</topic><topic>Adrenergic receptors</topic><topic>Animals</topic><topic>Ca2+-transporting ATPase</topic><topic>Calcium (intracellular)</topic><topic>Calcium (reticular)</topic><topic>Calcium - metabolism</topic><topic>Calcium influx</topic><topic>Calcium Signaling</topic><topic>Cyclopiazonic acid</topic><topic>Dehydrogenases</topic><topic>Endoplasmic reticulum</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>Fluorometry</topic><topic>Homeostasis</topic><topic>Kinases</topic><topic>Metabolic syndrome</topic><topic>Mice</topic><topic>Mitochondria</topic><topic>Photonics</topic><topic>Physiology</topic><topic>Protein turnover</topic><topic>Proteins</topic><topic>Thermogenesis</topic><topic>Transient Receptor Potential Channels - metabolism</topic><topic>Transient receptor potential proteins</topic><topic>Triglycerides</topic><topic>TRPC Cation Channels - metabolism</topic><topic>TRPC6 Cation Channel - metabolism</topic><topic>Uncoupling protein 1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hayato, R</creatorcontrib><creatorcontrib>Matsumoto, T</creatorcontrib><creatorcontrib>Higure, Y</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>Docstoc</collection><collection>University Readers</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>East Europe, Central Europe Database</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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 Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Physiological research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hayato, R</au><au>Matsumoto, T</au><au>Higure, Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ca2+ Depletion in the ER Causes Store-Operated Ca2+ Entry via the TRPC6 Channel in Mouse Brown Adipocytes</atitle><jtitle>Physiological research</jtitle><addtitle>Physiol Res</addtitle><date>2024-03-11</date><risdate>2024</risdate><volume>73</volume><issue>1</issue><spage>69</spage><epage>80</epage><pages>69-80</pages><issn>0862-8408</issn><eissn>1802-9973</eissn><abstract>beta3-adrenergic activation causes Ca2+ release from the mitochondria and subsequent Ca2+ release from the endoplasmic reticulum (ER), evoking store-operated Ca2+ entry (SOCE) due to Ca2+ depletion from the ER in mouse brown adipocytes. In this study, we investigated how Ca2+ depletion from the ER elicits SOCE in mouse brown adipocytes using fluorometry of intracellular Ca2+ concentration ([Ca2+]i). The administration of cyclopiazonic acid (CPA), a reversible sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump blocker in the ER, caused an increase in [Ca2+]i. Moreover, CPA induced SOCE was suppressed by the administration of a Ca2+ free Krebs solution and the transient receptor potential canonical 6 (TRPC6) selective blockers 2-APB, ML-9 and GsMTx-4 but not Pico145, which blocks TRPC1/4/5. Administration of TRPC6 channel agonist 1-oleoyl-2-acetyl-sn-glycerol (OAG) and flufenamic acid elicited Ca2+ entry. Moreover, our RT-PCR analyses detected mRNAs for TRPC6 in brown adipose tissues. In addition, western blot analyses showed the expression of the TRPC6 protein. Thus, TRPC6 is one of the Ca2+ pathways involved in SOCE. These modes of Ca2+ entry provide the basis for heat production via activation of Ca2+-dependent dehydrogenase and the expression of uncoupling protein 1 (UCP1). Enhancing thermogenic metabolism in brown adipocytes may serve as broad therapeutic utility to reduce obesity and metabolic syndrome.</abstract><cop>Czech Republic</cop><pub>Institute of Physiology</pub><pmid>38466006</pmid><doi>10.33549/physiolres.935071</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipocytes Adipocytes, Brown - metabolism Adipose tissue Adrenergic receptors Animals Ca2+-transporting ATPase Calcium (intracellular) Calcium (reticular) Calcium - metabolism Calcium influx Calcium Signaling Cyclopiazonic acid Dehydrogenases Endoplasmic reticulum Endoplasmic Reticulum - metabolism Fluorometry Homeostasis Kinases Metabolic syndrome Mice Mitochondria Photonics Physiology Protein turnover Proteins Thermogenesis Transient Receptor Potential Channels - metabolism Transient receptor potential proteins Triglycerides TRPC Cation Channels - metabolism TRPC6 Cation Channel - metabolism Uncoupling protein 1 |
| title | Ca2+ Depletion in the ER Causes Store-Operated Ca2+ Entry via the TRPC6 Channel in Mouse Brown Adipocytes |
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