Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy
This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identif...
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| Veröffentlicht in: | International journal of molecular sciences 2023-10, Vol.24 (20), p.15376 |
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| creator | Nahum-Ankonina, Ortal Kurtzwald-Josefson, Efrat Ciechanover, Aaron Waldman, Maayan Shwartz-Rohaker, Orna Hochhauser, Edith Meyer, Sam J Aravot, Dan Phillip, Moshe Barac, Yaron D |
| description | This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7, indicating potential cardiac dysfunction. The mRNA levels of USP18 (deubiquitinating enzyme), PSMB8, and PSMB9 (proteasome β-subunits) were down-regulated in db/db mice, while the mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were down-regulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. The reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to the future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets. |
| doi_str_mv | 10.3390/ijms242015376 |
| format | Article |
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The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7, indicating potential cardiac dysfunction. The mRNA levels of USP18 (deubiquitinating enzyme), PSMB8, and PSMB9 (proteasome β-subunits) were down-regulated in db/db mice, while the mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were down-regulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. The reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to the future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms242015376</identifier><identifier>PMID: 37895057</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Age ; Cardiomyopathy ; Cardiovascular disease ; Cell cycle ; Comparative analysis ; Complications and side effects ; Development and progression ; Diabetes ; Enzymes ; Gene expression ; Genes ; Heart failure ; Insulin resistance ; Ligases ; Pathogenesis ; Proteins ; Quality control ; RNA ; RNA sequencing ; Type 2 diabetes ; Ubiquitin</subject><ispartof>International journal of molecular sciences, 2023-10, Vol.24 (20), p.15376</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-e7c90b4456be168d44b4f2233b45fb8354b5da5d10187976567bb4abf9a7020a3</citedby><cites>FETCH-LOGICAL-c460t-e7c90b4456be168d44b4f2233b45fb8354b5da5d10187976567bb4abf9a7020a3</cites><orcidid>0000-0001-6887-815X ; 0000-0002-4688-2358</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607702/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607702/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Nahum-Ankonina, Ortal</creatorcontrib><creatorcontrib>Kurtzwald-Josefson, Efrat</creatorcontrib><creatorcontrib>Ciechanover, Aaron</creatorcontrib><creatorcontrib>Waldman, Maayan</creatorcontrib><creatorcontrib>Shwartz-Rohaker, Orna</creatorcontrib><creatorcontrib>Hochhauser, Edith</creatorcontrib><creatorcontrib>Meyer, Sam J</creatorcontrib><creatorcontrib>Aravot, Dan</creatorcontrib><creatorcontrib>Phillip, Moshe</creatorcontrib><creatorcontrib>Barac, Yaron D</creatorcontrib><title>Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy</title><title>International journal of molecular sciences</title><description>This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. 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Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.</description><subject>Age</subject><subject>Cardiomyopathy</subject><subject>Cardiovascular disease</subject><subject>Cell cycle</subject><subject>Comparative analysis</subject><subject>Complications and side effects</subject><subject>Development and progression</subject><subject>Diabetes</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Heart failure</subject><subject>Insulin resistance</subject><subject>Ligases</subject><subject>Pathogenesis</subject><subject>Proteins</subject><subject>Quality control</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>Type 2 diabetes</subject><subject>Ubiquitin</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkUtr3DAQgEVpyKs59m7opRcno7d9KmHTpguBhKQ5C8keJ1psayPZhf331bKh7YagwwjNN59mGEI-UzjnvIYLvxoSEwyo5Fp9IMdUMFYCKP3xv_sROUlpBcA4k_UhOeK6qiVIfUwWj86_zH7yY3EXw4Q2hQGLh02acCjuQ49Fzlx563DCVC7Hdm6wLRY2tj4Mm7C20_PmEznobJ_w7DWekscf338tfpY3t9fLxeVN2QgFU4m6qcEJIZVDqqpWCCc6xjh3Qnau4lI42VrZUqCVrrWSSjsnrOtqq4GB5afk2867nt2AbYPjFG1v1tEPNm5MsN7sZ0b_bJ7Cb0NBgc6ObPj6aojhZcY0mcGnBvvejhjmZFiV29BUCZHRL2_QVZjjmOfbUkxqxQX9Rz3ZHo0fu5A_brZSc6k1rSlokJk6f4fKp8XBN2HEzuf3vYJyV9DEkFLE7u-QFMx27WZv7fwP4Cmc9g</recordid><startdate>20231001</startdate><enddate>20231001</enddate><creator>Nahum-Ankonina, Ortal</creator><creator>Kurtzwald-Josefson, Efrat</creator><creator>Ciechanover, Aaron</creator><creator>Waldman, Maayan</creator><creator>Shwartz-Rohaker, Orna</creator><creator>Hochhauser, Edith</creator><creator>Meyer, Sam J</creator><creator>Aravot, Dan</creator><creator>Phillip, Moshe</creator><creator>Barac, Yaron D</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6887-815X</orcidid><orcidid>https://orcid.org/0000-0002-4688-2358</orcidid></search><sort><creationdate>20231001</creationdate><title>Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy</title><author>Nahum-Ankonina, Ortal ; Kurtzwald-Josefson, Efrat ; Ciechanover, Aaron ; Waldman, Maayan ; Shwartz-Rohaker, Orna ; Hochhauser, Edith ; Meyer, Sam J ; Aravot, Dan ; Phillip, Moshe ; Barac, Yaron D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-e7c90b4456be168d44b4f2233b45fb8354b5da5d10187976567bb4abf9a7020a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Age</topic><topic>Cardiomyopathy</topic><topic>Cardiovascular disease</topic><topic>Cell cycle</topic><topic>Comparative analysis</topic><topic>Complications and side effects</topic><topic>Development and progression</topic><topic>Diabetes</topic><topic>Enzymes</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Heart failure</topic><topic>Insulin resistance</topic><topic>Ligases</topic><topic>Pathogenesis</topic><topic>Proteins</topic><topic>Quality control</topic><topic>RNA</topic><topic>RNA sequencing</topic><topic>Type 2 diabetes</topic><topic>Ubiquitin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nahum-Ankonina, Ortal</creatorcontrib><creatorcontrib>Kurtzwald-Josefson, Efrat</creatorcontrib><creatorcontrib>Ciechanover, Aaron</creatorcontrib><creatorcontrib>Waldman, Maayan</creatorcontrib><creatorcontrib>Shwartz-Rohaker, Orna</creatorcontrib><creatorcontrib>Hochhauser, Edith</creatorcontrib><creatorcontrib>Meyer, Sam J</creatorcontrib><creatorcontrib>Aravot, Dan</creatorcontrib><creatorcontrib>Phillip, Moshe</creatorcontrib><creatorcontrib>Barac, Yaron D</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest Central</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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 China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nahum-Ankonina, Ortal</au><au>Kurtzwald-Josefson, Efrat</au><au>Ciechanover, Aaron</au><au>Waldman, Maayan</au><au>Shwartz-Rohaker, Orna</au><au>Hochhauser, Edith</au><au>Meyer, Sam J</au><au>Aravot, Dan</au><au>Phillip, Moshe</au><au>Barac, Yaron D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy</atitle><jtitle>International journal of molecular sciences</jtitle><date>2023-10-01</date><risdate>2023</risdate><volume>24</volume><issue>20</issue><spage>15376</spage><pages>15376-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. 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| subjects | Age Cardiomyopathy Cardiovascular disease Cell cycle Comparative analysis Complications and side effects Development and progression Diabetes Enzymes Gene expression Genes Heart failure Insulin resistance Ligases Pathogenesis Proteins Quality control RNA RNA sequencing Type 2 diabetes Ubiquitin |
| title | Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy |
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