Follistatin-like protein 1 attenuates doxorubicin-induced cardiomyopathy by inhibiting MsrB2-mediated mitophagy
Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from...
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| Veröffentlicht in: | Molecular and cellular biochemistry 2024-07, Vol.479 (7), p.1817-1831 |
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| creator | Lu, Linhe Shao, Yalan Wang, Nisha Xiong, Xiang Zhai, Mengen Tang, Jiayou Liu, Yang Yang, Jian Yang, Lifang |
| description | Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from diverse cardiac diseases, such as myocardial infarction, cardiac ischemia/reperfusion injury, and heart failure. However, its role in DOX-induced cardiomyopathy is unclear. Therefore, the present study investigated whether administering recombinant FSTL1 could mitigate DOX-induced cardiomyopathy and clarified the underlying molecular mechanisms. FSTL1 treatment attenuated DOX-induced cardiac dysfunction, cardiac fibrosis, and cellular apoptosis by inhibiting excess mitochondrial matrix protein methionine sulfoxide reductase B2 (MsrB2)-mediated mitophagy. Furthermore, FSTL1 administration reduced the expression of apoptotic proteins, including MsrB2, Bax, caspase 3, mitochondrial Parkin, and LC3-II, increased myocardial ATP content, and decreased cardiac malondialdehyde levels, thus protecting mitochondrial function against DOX-induced cardiac injury. Furthermore, FSTL1 treatment protected the contractile properties of adult cardiomyocytes against DOX-induced injury
in vitro
. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy. |
| doi_str_mv | 10.1007/s11010-024-04955-9 |
| format | Article |
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in vitro
. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy.</description><identifier>ISSN: 0300-8177</identifier><identifier>ISSN: 1573-4919</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-024-04955-9</identifier><identifier>PMID: 38696001</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; Cancer Research ; Carbonyl compounds ; Carbonyls ; Cardiology ; Cardiomyocytes ; Cardiomyopathy ; Cardiotoxicity ; Caspase-3 ; Congestive heart failure ; Coronary artery disease ; Doxorubicin ; Fibrosis ; Follistatin ; Health services ; Heart diseases ; Injury prevention ; Ischemia ; Life Sciences ; Matrix protein ; Medical Biochemistry ; Methionine ; Mitochondria ; Mitophagy ; Molecular modelling ; Muscle contraction ; Myocardial infarction ; Pathogenesis ; Pharmacology ; Proteins ; Reductases ; Reperfusion</subject><ispartof>Molecular and cellular biochemistry, 2024-07, Vol.479 (7), p.1817-1831</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-3ac88e79a385434044c84bb54253dce5ef197fadc89392a0be0980327f3da4e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11010-024-04955-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11010-024-04955-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38696001$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Linhe</creatorcontrib><creatorcontrib>Shao, Yalan</creatorcontrib><creatorcontrib>Wang, Nisha</creatorcontrib><creatorcontrib>Xiong, Xiang</creatorcontrib><creatorcontrib>Zhai, Mengen</creatorcontrib><creatorcontrib>Tang, Jiayou</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Yang, Jian</creatorcontrib><creatorcontrib>Yang, Lifang</creatorcontrib><title>Follistatin-like protein 1 attenuates doxorubicin-induced cardiomyopathy by inhibiting MsrB2-mediated mitophagy</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><addtitle>Mol Cell Biochem</addtitle><description>Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from diverse cardiac diseases, such as myocardial infarction, cardiac ischemia/reperfusion injury, and heart failure. However, its role in DOX-induced cardiomyopathy is unclear. Therefore, the present study investigated whether administering recombinant FSTL1 could mitigate DOX-induced cardiomyopathy and clarified the underlying molecular mechanisms. FSTL1 treatment attenuated DOX-induced cardiac dysfunction, cardiac fibrosis, and cellular apoptosis by inhibiting excess mitochondrial matrix protein methionine sulfoxide reductase B2 (MsrB2)-mediated mitophagy. Furthermore, FSTL1 administration reduced the expression of apoptotic proteins, including MsrB2, Bax, caspase 3, mitochondrial Parkin, and LC3-II, increased myocardial ATP content, and decreased cardiac malondialdehyde levels, thus protecting mitochondrial function against DOX-induced cardiac injury. Furthermore, FSTL1 treatment protected the contractile properties of adult cardiomyocytes against DOX-induced injury
in vitro
. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy.</description><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer Research</subject><subject>Carbonyl compounds</subject><subject>Carbonyls</subject><subject>Cardiology</subject><subject>Cardiomyocytes</subject><subject>Cardiomyopathy</subject><subject>Cardiotoxicity</subject><subject>Caspase-3</subject><subject>Congestive heart failure</subject><subject>Coronary artery disease</subject><subject>Doxorubicin</subject><subject>Fibrosis</subject><subject>Follistatin</subject><subject>Health services</subject><subject>Heart diseases</subject><subject>Injury prevention</subject><subject>Ischemia</subject><subject>Life Sciences</subject><subject>Matrix protein</subject><subject>Medical Biochemistry</subject><subject>Methionine</subject><subject>Mitochondria</subject><subject>Mitophagy</subject><subject>Molecular modelling</subject><subject>Muscle contraction</subject><subject>Myocardial infarction</subject><subject>Pathogenesis</subject><subject>Pharmacology</subject><subject>Proteins</subject><subject>Reductases</subject><subject>Reperfusion</subject><issn>0300-8177</issn><issn>1573-4919</issn><issn>1573-4919</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kUFvFSEUhYnR2NfqH3BhSNy4QS8D8waW2lhr0sZNuyYM3HmPOjM8gUk6_17qq5q46AZI-M65cA4hbzh84ADdx8w5cGDQSAZSty3Tz8iGt51gUnP9nGxAADDFu-6EnOZ8B5UGzl-SE6G2elvPGxIv4jiGXGwJMxvDD6SHFAuGmXJqS8F5sQUz9fE-pqUPrlJh9otDT51NPsRpjQdb9ivtVxrmfehDddrR65w-N2xCH6re0ymUeNjb3fqKvBjsmPH1435Gbi--3JxfsqvvX7-df7piTjTbwoR1SmGnrVCtFBKkdEr2fSubVniHLQ5cd4P1TmmhGws9glYgmm4Q3koU4oy8P_rW7_xcMBczhexwHO2McclGQAu8UzWOir77D72LS5rr6yqlGuB11ZVqjpRLMeeEgzmkMNm0Gg7moQ5zrMPUOszvOsyD6O2j9dLXLP5K_uRfAXEEcr2ad5j-zX7C9hfbPZZc</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>Lu, Linhe</creator><creator>Shao, Yalan</creator><creator>Wang, Nisha</creator><creator>Xiong, Xiang</creator><creator>Zhai, Mengen</creator><creator>Tang, Jiayou</creator><creator>Liu, Yang</creator><creator>Yang, Jian</creator><creator>Yang, Lifang</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20240701</creationdate><title>Follistatin-like protein 1 attenuates doxorubicin-induced cardiomyopathy by inhibiting MsrB2-mediated mitophagy</title><author>Lu, Linhe ; 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however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from diverse cardiac diseases, such as myocardial infarction, cardiac ischemia/reperfusion injury, and heart failure. However, its role in DOX-induced cardiomyopathy is unclear. Therefore, the present study investigated whether administering recombinant FSTL1 could mitigate DOX-induced cardiomyopathy and clarified the underlying molecular mechanisms. FSTL1 treatment attenuated DOX-induced cardiac dysfunction, cardiac fibrosis, and cellular apoptosis by inhibiting excess mitochondrial matrix protein methionine sulfoxide reductase B2 (MsrB2)-mediated mitophagy. Furthermore, FSTL1 administration reduced the expression of apoptotic proteins, including MsrB2, Bax, caspase 3, mitochondrial Parkin, and LC3-II, increased myocardial ATP content, and decreased cardiac malondialdehyde levels, thus protecting mitochondrial function against DOX-induced cardiac injury. Furthermore, FSTL1 treatment protected the contractile properties of adult cardiomyocytes against DOX-induced injury
in vitro
. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38696001</pmid><doi>10.1007/s11010-024-04955-9</doi><tpages>15</tpages></addata></record> |
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| subjects | Apoptosis Biochemistry Biomedical and Life Sciences Cancer Research Carbonyl compounds Carbonyls Cardiology Cardiomyocytes Cardiomyopathy Cardiotoxicity Caspase-3 Congestive heart failure Coronary artery disease Doxorubicin Fibrosis Follistatin Health services Heart diseases Injury prevention Ischemia Life Sciences Matrix protein Medical Biochemistry Methionine Mitochondria Mitophagy Molecular modelling Muscle contraction Myocardial infarction Pathogenesis Pharmacology Proteins Reductases Reperfusion |
| title | Follistatin-like protein 1 attenuates doxorubicin-induced cardiomyopathy by inhibiting MsrB2-mediated mitophagy |
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