caa a22 4500 606233563 CHVBK 20210128101232.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s11010-015-2383-5 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2383-5 Hydrogen sulfide mitigates homocysteine-mediated pathological remodeling by inducing miR-133a in cardiomyocytes [Elektronische Daten] [Varun Kesherwani, Shyam Nandi, Surender Sharawat, Hamid Shahshahan, Paras Mishra] An elevated level of homocysteine called hyperhomocysteinemia (HHcy) is associated with pathological cardiac remodeling. Hydrogen sulfide (H2S) acts as a cardioprotective gas; however, the mechanism by which H2S mitigates homocysteine-mediated pathological remodeling in cardiomyocytes is unclear. We hypothesized that H2S ameliorates HHcy-mediated hypertrophy by inducing cardioprotective miR-133a in cardiomyocytes. To test the hypothesis, HL1 cardiomyocytes were treated with (1) plain medium (control, CT), (2) 100µM of homocysteine (Hcy), (3) Hcy with 30µM of H2S (Hcy+H2S), and (4) H2S for 24h. The levels of hypertrophy markers: c-fos, atrial natriuretic peptide (ANP), and beta-myosin heavy chain (β-MHC), miR-133a, and its transcriptional inducer myosin enhancer factor-2C (MEF2C) were determined by Western blotting, RT-qPCR, and immunofluorescence. The activity of MEF2C was assessed by co-immunoprecipitation of MEF2C with histone deacetylase-1(HDAC1). Our results show that H2S ameliorates homocysteine-mediated up-regulation of c-fos, ANP, and β-MHC, and down-regulation of MEF2C and miR-133a. HHcy induces the binding of MEF2C with HDAC1, whereas H2S releases MEF2C from MEF2C-HDAC1 complex causing activation of MEF2C. These findings elicit that HHcy induces cardiac hypertrophy by promoting MEF2C-HDAC1 complex formation that inactivates MEF2C causing suppression of anti-hypertrophy miR-133a in cardiomyocytes. H2S mitigates hypertrophy by inducing miR-133a through activation of MEF2C in HHcy cardiomyocytes. To our knowledge, this is a novel mechanism of H2S-mediated activation of MEF2C and induction of miR-133a and inhibition of hypertrophy in HHcy cardiomyocytes. Springer Science+Business Media New York, 2015 Hyperhomocysteinemia nationallicence Hydrogen sulfide nationallicence MiR-133a nationallicence Hypertrophy nationallicence MEF2C nationallicence HDAC nationallicence HHcy : Hyperhomocysteinemia nationallicence H2S : Hydrogen sulfide nationallicence Hcy : Homocysteine nationallicence ANP : Atrial natriuretic peptide nationallicence β-MHC : Beta-myosin heavy chain nationallicence MEF2C : Myosin-specific enhancer factor 2C nationallicence Kesherwani Varun Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut Nandi Shyam Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut Sharawat Surender Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut Shahshahan Hamid Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut Mishra Paras Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 241-250 0300-8177 404:1-2<241 2015 404 11010 https://doi.org/10.1007/s11010-015-2383-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2383-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kesherwani Varun Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut NATIONALLICENCE 700 1- Nandi Shyam Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut NATIONALLICENCE 700 1- Sharawat Surender Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut NATIONALLICENCE 700 1- Shahshahan Hamid Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut NATIONALLICENCE 700 1- Mishra Paras Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 668 S 41st Street, DRC1, Room 5047, 68198-5850, Omaha, NE, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 241-250 0300-8177 404:1-2<241 2015 404 11010