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Sökning: WFRF:(Agarwal Prasoon) > Mitochondrial Sirtu...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006711naa a2200529 4500
001oai:DiVA.org:kth-313069
003SwePub
008220530s2022 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3130692 URI
0247 a https://doi.org/10.1161/CIRCHEARTFAILURE.121.0085472 DOI
040 a (SwePub)kth
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Tomczyk, Mateusz M.u Childrens Hosp Res Inst Manitoba, Diabet Res Envisioned & Accomplished Manitoba DRE, Winnipeg, MB, Canada.;Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Manitoba, Coll Med, Rady Fac Hlth Sci, Winnipeg, MB, Canada.4 aut
2451 0a Mitochondrial Sirtuin-3 (SIRT3) Prevents Doxorubicin-Induced Dilated Cardiomyopathy by Modulating Protein Acetylation and Oxidative Stress
264 1b Ovid Technologies (Wolters Kluwer Health),c 2022
338 a print2 rdacarrier
500 a QC 20220530
520 a Background: High doses of doxorubicin put cancer patients at risk for developing dilated cardiomyopathy. Previously, we showed that doxorubicin treatment decreases SIRT3 (sirtuin 3), the main mitochondrial deacetylase and increases protein acetylation in rat cardiomyocytes. Here, we hypothesize that SIRT3 expression can attenuate doxorubicin induced dilated cardiomyopathy in vivo by preventing the acetylation of mitochondrial proteins. Methods: Nontransgenic, M3-SIRT3 (truncated SIRT3; short isoform), and M1-SIRT3 (full-length SIRT3; mitochondrial localized) transgenic mice were treated with doxorubicin for 4 weeks (8 mg/kg body weight per week). Echocardiography was performed to assess cardiac structure and function and validated by immunohistochemistry and immunofluorescence (n=4-10). Mass spectrometry was performed on cardiac mitochondrial peptides in saline (n=6) and doxorubicin (n=5) treated hearts. Validation was performed in doxorubicin treated primary rat and human induced stem cell derived cardiomyocytes transduced with adenoviruses for M3-SIRT3 and M1-SIRT3 and deacetylase deficient mutants (n=4-10). Results: Echocardiography revealed that M3-SIRT3 transgenic mice were partially resistant to doxorubicin induced changes to cardiac structure and function whereas M1-SIRT3 expression prevented cardiac remodeling and dysfunction. In doxorubicin hearts, 37 unique acetylation sites on mitochondrial proteins were altered. Pathway analysis revealed these proteins are involved in energy production, fatty acid metabolism, and oxidative stress resistance. Increased M1-SIRT3 expression in primary rat and human cardiomyocytes attenuated doxorubicin-induced superoxide formation, whereas deacetylase deficient mutants were unable to prevent oxidative stress. Conclusions: Doxorubicin reduced SIRT3 expression and markedly affected the cardiac mitochondrial acetylome. Increased M1-SIRT3 expression in vivo prevented doxorubicin-induced cardiac dysfunction, suggesting that SIRT3 could be a potential therapeutic target for mitigating doxorubicin-induced dilated cardiomyopathy.
650 7a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologi0 (SwePub)3042 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Medical Biotechnology0 (SwePub)3042 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Oto-rhino-laryngologi0 (SwePub)302182 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Otorhinolaryngology0 (SwePub)302182 hsv//eng
653 a acetylation
653 a dilated cardiomyopathy
653 a doxorubicin
653 a mitochondria
653 a superoxide
7001 a Cheung, Kyle G.u Childrens Hosp Res Inst Manitoba, Diabet Res Envisioned & Accomplished Manitoba DRE, Winnipeg, MB, Canada.;Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Manitoba, Coll Med, Rady Fac Hlth Sci, Winnipeg, MB, Canada.4 aut
7001 a Xiang, Bou Childrens Hosp Res Inst Manitoba, Diabet Res Envisioned & Accomplished Manitoba DRE, Winnipeg, MB, Canada.;Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Manitoba, Coll Med, Rady Fac Hlth Sci, Winnipeg, MB, Canada.4 aut
7001 a Tamanna, Nahidu Univ Manitoba, Dept Biol Sci, Winnipeg, MB, Canada.4 aut
7001 a Teixeira, Ana L. Fonsecau Univ Manitoba, Dept Biol Sci, Winnipeg, MB, Canada.4 aut
7001 a Agarwal, Prasoonu KTH,Beräkningsvetenskap och beräkningsteknik (CST),Science for Life Laboratory, SciLifeLab,Childrens Hosp Res Inst Manitoba, Diabet Res Envisioned & Accomplished Manitoba DRE, Winnipeg, MB, Canada.;Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Manitoba, Coll Med, Rady Fac Hlth Sci, Winnipeg, MB, Canada.4 aut0 (Swepub:kth)u1w12f9s
7001 a Kereliuk, Stephanie M.u Childrens Hosp Res Inst Manitoba, Diabet Res Envisioned & Accomplished Manitoba DRE, Winnipeg, MB, Canada.;Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Manitoba, Coll Med, Rady Fac Hlth Sci, Winnipeg, MB, Canada.4 aut
7001 a Spicer, Victoru Univ Manitoba, Dept Internal Med, Winnipeg, MB, Canada.;Univ Manitoba, Coll Med, Rady Fac Hlth Sci, Winnipeg, MB, Canada.;Manitoba Ctr Prote & Syst Biol, Winnipeg, MB, Canada.4 aut
7001 a Lin, Ligenu Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA.;Univ Macau, Inst Chinese Med Sci, Taipa, Macao, Peoples R China.4 aut
7001 a Treberg, Jasonu Univ Manitoba, Dept Biol Sci, Winnipeg, MB, Canada.4 aut
7001 a Tong, Qiangu Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA.4 aut
7001 a Dolinsky, Vernon W.u Childrens Hosp Res Inst Manitoba, Diabet Res Envisioned & Accomplished Manitoba DRE, Winnipeg, MB, Canada.;Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Manitoba, Coll Med, Rady Fac Hlth Sci, Winnipeg, MB, Canada.4 aut
7102 a Childrens Hosp Res Inst Manitoba, Diabet Res Envisioned & Accomplished Manitoba DRE, Winnipeg, MB, Canada.;Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.;Univ Manitoba, Coll Med, Rady Fac Hlth Sci, Winnipeg, MB, Canada.b Univ Manitoba, Dept Biol Sci, Winnipeg, MB, Canada.4 org
7730 t Circulation Heart Failured : Ovid Technologies (Wolters Kluwer Health)g 15:5q 15:5x 1941-3289x 1941-3297
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-313069
8564 8u https://doi.org/10.1161/CIRCHEARTFAILURE.121.008547

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