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Protein tyrosine phosphatase 1B regulates miR-208b-argonaute 2 association and thyroid hormone responsiveness in cardiac hypertrophy.
Coulis, Gérald; Londhe, Avinash D; Sagabala, R Sudheer; Shi, Yanfen; Labbé, David P; Bergeron, Alexandre; Sahadevan, Pramod; Nawaito, Sherin A; Sahmi, Fatiha; Josse, Marie; Vinette, Valérie; Guertin, Marie-Claude; Karsenty, Gérard; Tremblay, Michel L; Tardif, Jean-Claude; Allen, Bruce G; Boivin, Benoit.
Afiliación
  • Coulis G; Department of Nanobioscience, College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, USA.
  • Londhe AD; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
  • Sagabala RS; Department of Nanobioscience, College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, USA.
  • Shi Y; Department of Nanobioscience, College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, USA.
  • Labbé DP; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
  • Bergeron A; Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Sahadevan P; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
  • Nawaito SA; Department of Surgery, Division of Urology, McGill University, Montreal, QC H3G 1Y6, Canada.
  • Sahmi F; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
  • Josse M; Department of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
  • Vinette V; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
  • Guertin MC; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada.
  • Karsenty G; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
  • Tremblay ML; Pharmacology and Physiology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
  • Tardif JC; Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
  • Allen BG; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
  • Boivin B; Department of Nanobioscience, College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, USA.
Sci Signal ; 15(730): eabn6875, 2022 04 19.
Article en En | MEDLINE | ID: mdl-35439023
Increased production of reactive oxygen species plays an essential role in the pathogenesis of several diseases, including cardiac hypertrophy. In our search to identify redox-sensitive targets that contribute to redox signaling, we found that protein tyrosine phosphatase 1B (PTP1B) was reversibly oxidized and inactivated in hearts undergoing hypertrophy. Cardiomyocyte-specific deletion of PTP1B in mice (PTP1B cKO mice) caused a hypertrophic phenotype that was exacerbated by pressure overload. Furthermore, we showed that argonaute 2 (AGO2), a key component of the RNA-induced silencing complex, was a substrate of PTP1B in cardiomyocytes and in the heart. Our results revealed that phosphorylation at Tyr393 and inactivation of AGO2 in PTP1B cKO mice prevented miR-208b-mediated repression of thyroid hormone receptor-associated protein 1 (THRAP1; also known as MED13) and contributed to thyroid hormone-mediated cardiac hypertrophy. In support of this conclusion, inhibiting the synthesis of triiodothyronine (T3) with propylthiouracil rescued pressure overload-induced hypertrophy and improved myocardial contractility and systolic function in PTP1B cKO mice. Together, our data illustrate that PTP1B activity is cardioprotective and that redox signaling is linked to thyroid hormone responsiveness and microRNA-mediated gene silencing in pathological hypertrophy.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: MicroARNs / Proteína Tirosina Fosfatasa no Receptora Tipo 1 Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: MicroARNs / Proteína Tirosina Fosfatasa no Receptora Tipo 1 Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos