{"corpus_id":36828715,"paper_sha":"a200842e8f89a27d1412fa7d0d6995303c605b79","doi":"10.2337/db16-0023","arxiv_id":null,"pmid":27411382,"pmcid":"5033264","mag_id":2467322882,"dblp_id":null,"acl_id":null,"title":"Lack of miR-133a Decreases Contractility of Diabetic Hearts: A Role for Novel Cross Talk Between Tyrosine Aminotransferase and Tyrosine Hydroxylase","year":2016,"publication_date":"2016-07-13","venue":"Diabetes","journal":{"name":"","pages":"3075 - 3090","volume":"65"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":55,"citation_count":48,"influential_citation_count":0,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Blotting, Western","mj":false,"ui":"D015153"},{"d":"Diabetes Mellitus, Experimental","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D003921"},{"d":"HEK293 Cells","mj":false,"ui":"D057809"},{"d":"Hemodynamics","mj":false,"qs":[{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D006439"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Immunohistochemistry","mj":false,"ui":"D007150"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Mice, Transgenic","mj":false,"ui":"D008822"},{"d":"MicroRNAs","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"},{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D035683"},{"d":"Myocardial Contraction","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D009200"},{"d":"Myocardium","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D009206"},{"d":"Myocytes, Cardiac","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D032383"},{"d":"Norepinephrine","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D009638"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Rats, Sprague-Dawley","mj":false,"ui":"D017207"},{"d":"Receptors, Adrenergic, beta","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D011943"},{"d":"Reverse Transcriptase Polymerase Chain Reaction","mj":false,"ui":"D020133"},{"d":"Tyrosine 3-Monooxygenase","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D014446"},{"d":"Tyrosine Transaminase","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D014444"}],"chemicals":[{"n":"MIRN133 microRNA, rat","ui":"C549446","reg":"0"},{"n":"MicroRNAs","ui":"D035683","reg":"0"},{"n":"Receptors, Adrenergic, beta","ui":"D011943","reg":"0"},{"n":"Tyrosine 3-Monooxygenase","ui":"D014446","reg":"EC 1.14.16.2"},{"n":"Tyrosine Transaminase","ui":"D014444","reg":"EC 2.6.1.5"},{"n":"Norepinephrine","ui":"D009638","reg":"X4W3ENH1CV"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://diabetes.diabetesjournals.org/content/diabetes/65/10/3075.full.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/a200842e8f89a27d1412fa7d0d6995303c605b79","s2_open_access_license":null,"s2_open_access_status":"BRONZE","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"MicroRNAs (miRNAs) have a fundamental role in diabetic heart failure. The cardioprotective miRNA-133a (miR-133a) is downregulated, and contractility is decreased in diabetic hearts. Norepinephrine (NE) is a key catecholamine that stimulates contractility by activating β-adrenergic receptors (β-AR). NE is synthesized from tyrosine by the rate-limiting enzyme, tyrosine hydroxylase (TH), and tyrosine is catabolized by tyrosine aminotransferase (TAT). However, the cross talk/link between TAT and TH in the heart is unclear. To determine whether miR-133a plays a role in the cross talk between TH and TAT and regulates contractility by influencing NE biosynthesis and/or β-AR levels in diabetic hearts, Sprague-Dawley rats and miR-133a transgenic (miR-133aTg) mice were injected with streptozotocin to induce diabetes. The diabetic rats were then treated with miR-133a mimic or scrambled miRNA. Our results revealed that miR-133a mimic treatment improved the contractility of the diabetic rat’s heart concomitant with upregulation of TH, cardiac NE, β-AR, and downregulation of TAT and plasma levels of NE. In miR-133aTg mice, cardiac-specific miR-133a overexpression prevented upregulation of TAT and suppression of TH in the heart after streptozotocin was administered. Moreover, miR-133a overexpression in CATH.a neuronal cells suppressed TAT with concomitant upregulation of TH, whereas knockdown and overexpression of TAT demonstrated that TAT inhibited TH. Luciferase reporter assay confirmed that miR-133a targets TAT. In conclusion, miR-133a controls the contractility of diabetic hearts by targeting TAT, regulating NE biosynthesis, and consequently, β-AR and cardiac function.","claims":[{"public_id":"cl_13606daca002e0f016fafc234a2458f5","status":"active","text":"A luciferase reporter assay confirms that miR-133a directly targets tyrosine aminotransferase.","confidence":0.9,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"}],"url":"https://sah.borca.ai/claims/cl_13606daca002e0f016fafc234a2458f5"},{"public_id":"cl_9657c8b610e9dbbe17c6a4ff5d608547","status":"active","text":"Cardiac-specific miR-133a overexpression in miR-133a transgenic 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