STIM2 knockdown protects against ischemia/reperfusion injury through reducing mitochondrial calcium overload and preserving mitochondrial function
Mitochondrial dysfunction caused by calcium overload is a vital factor for mediating cardiomyocyte death following ischemia/reperfusion (I/R) injury. The stromal interactive molecule 2 (STIM2) is a calcium sensor protein that regulates the store-operated calcium entry (SOCE). Whereas, whether STIM2...
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| Veröffentlicht in: | Life sciences (1973) 2020-04, Vol.247, p.116560-7, Article 116560 |
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| creator | Tu, Chen-chen Wan, Bao-yan Zeng, Yong |
| description | Mitochondrial dysfunction caused by calcium overload is a vital factor for mediating cardiomyocyte death following ischemia/reperfusion (I/R) injury. The stromal interactive molecule 2 (STIM2) is a calcium sensor protein that regulates the store-operated calcium entry (SOCE). Whereas, whether STIM2 is associated with I/R injury remains largely unclear. We report here that STIM2, but not its homologue STIM1, is upregulated in cultured H9c2 cells, a cell model for cardiomyocytes, following I/R injury. In addition, the knockdown of STIM2, but not STIM1, reduces H9c2 cell apoptosis following I/R injury, and similar results were obtained in primary neonatal cardiomyocytes. This anti-apoptotic effect could be attributed to the inhibited activation of mitochondrial apoptosis pathway. Moreover, STIM2 knockdown reduces ER calcium release and simultaneously alleviates mitochondrial calcium overload in H9c2 cells following I/R injury. Furthermore, STIM2 knockdown decreases mitochondrial injury and preserves mitochondrial function following I/R injury. Collectively, these results suggest that the protective role of STIM2 knockdown against I/R injury in cardiomyocytes is associated with the reduced mitochondrial calcium overload and preserved mitochondrial function. Hence, our study may provide a novel insight into the regulation of mitochondrial-mediated cardiomyocyte apoptosis following I/R injury. |
| doi_str_mv | 10.1016/j.lfs.2019.116560 |
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The stromal interactive molecule 2 (STIM2) is a calcium sensor protein that regulates the store-operated calcium entry (SOCE). Whereas, whether STIM2 is associated with I/R injury remains largely unclear. We report here that STIM2, but not its homologue STIM1, is upregulated in cultured H9c2 cells, a cell model for cardiomyocytes, following I/R injury. In addition, the knockdown of STIM2, but not STIM1, reduces H9c2 cell apoptosis following I/R injury, and similar results were obtained in primary neonatal cardiomyocytes. This anti-apoptotic effect could be attributed to the inhibited activation of mitochondrial apoptosis pathway. Moreover, STIM2 knockdown reduces ER calcium release and simultaneously alleviates mitochondrial calcium overload in H9c2 cells following I/R injury. Furthermore, STIM2 knockdown decreases mitochondrial injury and preserves mitochondrial function following I/R injury. Collectively, these results suggest that the protective role of STIM2 knockdown against I/R injury in cardiomyocytes is associated with the reduced mitochondrial calcium overload and preserved mitochondrial function. Hence, our study may provide a novel insight into the regulation of mitochondrial-mediated cardiomyocyte apoptosis following I/R injury.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2019.116560</identifier><identifier>PMID: 31200000</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Apoptosis ; Calcium ; Calcium (mitochondrial) ; Calcium - metabolism ; Calcium overload ; Cardiomyocytes ; Cell Line ; Gene Expression Regulation ; Gene Knockdown Techniques ; H9c2 cell ; Homology ; Injury prevention ; Ion Transport - physiology ; Ischemia ; Ischemia/reperfusion injury ; Mitochondria ; Mitochondria, Heart - metabolism ; Mitochondrial function ; Myocytes, Cardiac - metabolism ; Neonates ; Overloading ; Rats ; Reperfusion ; Reperfusion Injury - metabolism ; Reperfusion Injury - prevention & control ; RNA, Small Interfering ; STIM1 protein ; STIM2 ; Stromal Interaction Molecule 2 - genetics ; Stromal Interaction Molecule 2 - metabolism ; Transfection</subject><ispartof>Life sciences (1973), 2020-04, Vol.247, p.116560-7, Article 116560</ispartof><rights>2019 Elsevier Inc.</rights><rights>Copyright © 2019 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier BV 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-61f9437a76ca6205950f2b9d462b09958cf8b68555e1c0ab92fc0ebd6b49e3553</citedby><cites>FETCH-LOGICAL-c381t-61f9437a76ca6205950f2b9d462b09958cf8b68555e1c0ab92fc0ebd6b49e3553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0024320519304862$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31200000$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tu, Chen-chen</creatorcontrib><creatorcontrib>Wan, Bao-yan</creatorcontrib><creatorcontrib>Zeng, Yong</creatorcontrib><title>STIM2 knockdown protects against ischemia/reperfusion injury through reducing mitochondrial calcium overload and preserving mitochondrial function</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Mitochondrial dysfunction caused by calcium overload is a vital factor for mediating cardiomyocyte death following ischemia/reperfusion (I/R) injury. The stromal interactive molecule 2 (STIM2) is a calcium sensor protein that regulates the store-operated calcium entry (SOCE). Whereas, whether STIM2 is associated with I/R injury remains largely unclear. We report here that STIM2, but not its homologue STIM1, is upregulated in cultured H9c2 cells, a cell model for cardiomyocytes, following I/R injury. In addition, the knockdown of STIM2, but not STIM1, reduces H9c2 cell apoptosis following I/R injury, and similar results were obtained in primary neonatal cardiomyocytes. This anti-apoptotic effect could be attributed to the inhibited activation of mitochondrial apoptosis pathway. Moreover, STIM2 knockdown reduces ER calcium release and simultaneously alleviates mitochondrial calcium overload in H9c2 cells following I/R injury. Furthermore, STIM2 knockdown decreases mitochondrial injury and preserves mitochondrial function following I/R injury. Collectively, these results suggest that the protective role of STIM2 knockdown against I/R injury in cardiomyocytes is associated with the reduced mitochondrial calcium overload and preserved mitochondrial function. Hence, our study may provide a novel insight into the regulation of mitochondrial-mediated cardiomyocyte apoptosis following I/R injury.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Calcium</subject><subject>Calcium (mitochondrial)</subject><subject>Calcium - metabolism</subject><subject>Calcium overload</subject><subject>Cardiomyocytes</subject><subject>Cell Line</subject><subject>Gene Expression Regulation</subject><subject>Gene Knockdown Techniques</subject><subject>H9c2 cell</subject><subject>Homology</subject><subject>Injury prevention</subject><subject>Ion Transport - physiology</subject><subject>Ischemia</subject><subject>Ischemia/reperfusion injury</subject><subject>Mitochondria</subject><subject>Mitochondria, Heart - metabolism</subject><subject>Mitochondrial function</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Neonates</subject><subject>Overloading</subject><subject>Rats</subject><subject>Reperfusion</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - prevention & control</subject><subject>RNA, Small Interfering</subject><subject>STIM1 protein</subject><subject>STIM2</subject><subject>Stromal Interaction Molecule 2 - genetics</subject><subject>Stromal Interaction Molecule 2 - metabolism</subject><subject>Transfection</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9vFCEYh4nR2LX6AbwYEi9eZsufgRniyTRam9R4sJ4JA-_ssp2BFYY1_Rp-4rLZ6kETuXB53h_83geh15SsKaHyYreexrxmhKo1pVJI8gStaN-phkhOn6IVIaxtOCPiDL3IeUcIEaLjz9EZp4wczwr9-nZ7_YXhuxDtnYs_A96nuIBdMjYb40NesM92C7M3Fwn2kMaSfQzYh11J93jZplg2W5zAFevDBs9-iXYbg0veTNiayfoy43iANEXjsAmuPgAZ0uFfeizBLjX8JXo2minDq8f7HH3_9PH28nNz8_Xq-vLDTWN5T5dG0lG1vDOdtEbWjkqQkQ3KtZINRCnR27EfZC-EAGqJGRQbLYHByaFVwIXg5-jdKbdW_lEgL3quXWGaTIBYsma8JYSrTpGKvv0L3cWSQv2dZi1XrO-79hhIT5RNMecEo94nP5t0rynRR2F6p6swfRSmT8LqzJvH5DLM4P5M_DZUgfcnAOoqDh6SztZDsOB8qp60i_4_8Q8eu6kQ</recordid><startdate>20200415</startdate><enddate>20200415</enddate><creator>Tu, Chen-chen</creator><creator>Wan, Bao-yan</creator><creator>Zeng, Yong</creator><general>Elsevier Inc</general><general>Elsevier BV</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20200415</creationdate><title>STIM2 knockdown protects against ischemia/reperfusion injury through reducing mitochondrial calcium overload and preserving mitochondrial function</title><author>Tu, Chen-chen ; Wan, Bao-yan ; Zeng, Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-61f9437a76ca6205950f2b9d462b09958cf8b68555e1c0ab92fc0ebd6b49e3553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Calcium</topic><topic>Calcium (mitochondrial)</topic><topic>Calcium - metabolism</topic><topic>Calcium overload</topic><topic>Cardiomyocytes</topic><topic>Cell Line</topic><topic>Gene Expression Regulation</topic><topic>Gene Knockdown Techniques</topic><topic>H9c2 cell</topic><topic>Homology</topic><topic>Injury prevention</topic><topic>Ion Transport - physiology</topic><topic>Ischemia</topic><topic>Ischemia/reperfusion injury</topic><topic>Mitochondria</topic><topic>Mitochondria, Heart - metabolism</topic><topic>Mitochondrial function</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Neonates</topic><topic>Overloading</topic><topic>Rats</topic><topic>Reperfusion</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - prevention & control</topic><topic>RNA, Small Interfering</topic><topic>STIM1 protein</topic><topic>STIM2</topic><topic>Stromal Interaction Molecule 2 - genetics</topic><topic>Stromal Interaction Molecule 2 - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tu, Chen-chen</creatorcontrib><creatorcontrib>Wan, Bao-yan</creatorcontrib><creatorcontrib>Zeng, Yong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tu, Chen-chen</au><au>Wan, Bao-yan</au><au>Zeng, Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>STIM2 knockdown protects against ischemia/reperfusion injury through reducing mitochondrial calcium overload and preserving mitochondrial function</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2020-04-15</date><risdate>2020</risdate><volume>247</volume><spage>116560</spage><epage>7</epage><pages>116560-7</pages><artnum>116560</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Mitochondrial dysfunction caused by calcium overload is a vital factor for mediating cardiomyocyte death following ischemia/reperfusion (I/R) injury. The stromal interactive molecule 2 (STIM2) is a calcium sensor protein that regulates the store-operated calcium entry (SOCE). Whereas, whether STIM2 is associated with I/R injury remains largely unclear. We report here that STIM2, but not its homologue STIM1, is upregulated in cultured H9c2 cells, a cell model for cardiomyocytes, following I/R injury. In addition, the knockdown of STIM2, but not STIM1, reduces H9c2 cell apoptosis following I/R injury, and similar results were obtained in primary neonatal cardiomyocytes. This anti-apoptotic effect could be attributed to the inhibited activation of mitochondrial apoptosis pathway. Moreover, STIM2 knockdown reduces ER calcium release and simultaneously alleviates mitochondrial calcium overload in H9c2 cells following I/R injury. Furthermore, STIM2 knockdown decreases mitochondrial injury and preserves mitochondrial function following I/R injury. 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| subjects | Animals Apoptosis Calcium Calcium (mitochondrial) Calcium - metabolism Calcium overload Cardiomyocytes Cell Line Gene Expression Regulation Gene Knockdown Techniques H9c2 cell Homology Injury prevention Ion Transport - physiology Ischemia Ischemia/reperfusion injury Mitochondria Mitochondria, Heart - metabolism Mitochondrial function Myocytes, Cardiac - metabolism Neonates Overloading Rats Reperfusion Reperfusion Injury - metabolism Reperfusion Injury - prevention & control RNA, Small Interfering STIM1 protein STIM2 Stromal Interaction Molecule 2 - genetics Stromal Interaction Molecule 2 - metabolism Transfection |
| title | STIM2 knockdown protects against ischemia/reperfusion injury through reducing mitochondrial calcium overload and preserving mitochondrial function |
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