PMID- 29385061 OWN - NLM STAT- MEDLINE DCOM- 20180907 LR - 20181202 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 2 DP - 2018 Jan 31 TI - HDAC Inhibition Improves the Sarcoendoplasmic Reticulum Ca(2+)-ATPase Activity in Cardiac Myocytes. LID - 10.3390/ijms19020419 [doi] LID - 419 AB - SERCA2a is the Ca(2+) ATPase playing the major contribution in cardiomyocyte (CM) calcium removal. Its activity can be regulated by both modulatory proteins and several post-translational modifications. The aim of the present work was to investigate whether the function of SERCA2 can be modulated by treating CMs with the histone deacetylase (HDAC) inhibitor suberanilohydroxamic acid (SAHA). The incubation with SAHA (2.5 microM, 90 min) of CMs isolated from rat adult hearts resulted in an increase of SERCA2 acetylation level and improved ATPase activity. This was associated with a significant improvement of calcium transient recovery time and cell contractility. Previous reports have identified K464 as an acetylation site in human SERCA2. Mutants were generated where K464 was substituted with glutamine (Q) or arginine (R), mimicking constitutive acetylation or deacetylation, respectively. The K464Q mutation ameliorated ATPase activity and calcium transient recovery time, thus indicating that constitutive K464 acetylation has a positive impact on human SERCA2a (hSERCA2a) function. In conclusion, SAHA induced deacetylation inhibition had a positive impact on CM calcium handling, that, at least in part, was due to improved SERCA2 activity. This observation can provide the basis for the development of novel pharmacological approaches to ameliorate SERCA2 efficiency. FAU - Meraviglia, Viviana AU - Meraviglia V AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). viviana.meraviglia@eurac.edu. FAU - Bocchi, Leonardo AU - Bocchi L AUID- ORCID: 0000-0003-4799-2804 AD - Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy. leonardo.bocchi@unipr.it. FAU - Sacchetto, Roberta AU - Sacchetto R AD - Department of Comparative Biomedicine and Food Science, University of Padova, 35020 Legnaro (Padova), Italy. roberta.sacchetto@unipd.it. FAU - Florio, Maria Cristina AU - Florio MC AUID- ORCID: 0000-0002-4524-926X AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). cristiflorio@gmail.com. FAU - Motta, Benedetta M AU - Motta BM AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). benedetta.motta@eurac.edu. FAU - Corti, Corrado AU - Corti C AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). corrado.corti@eurac.edu. FAU - Weichenberger, Christian X AU - Weichenberger CX AUID- ORCID: 0000-0002-2176-0274 AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). christian.weichenberger@eurac.edu. FAU - Savi, Monia AU - Savi M AUID- ORCID: 0000-0002-7895-7756 AD - Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy. monia.savi@unipr.it. FAU - D'Elia, Yuri AU - D'Elia Y AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). yuri.delia@eurac.edu. FAU - Rosato-Siri, Marcelo D AU - Rosato-Siri MD AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). Marcelo.RosatoSiri@eurac.edu. FAU - Suffredini, Silvia AU - Suffredini S AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). silvia.suffredini@alice.it. FAU - Piubelli, Chiara AU - Piubelli C AUID- ORCID: 0000-0002-5739-3795 AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). chiara.piubelli@sacrocuore.it. FAU - Pompilio, Giulio AU - Pompilio G AD - Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy. giulio.pompilio@ccfm.it. AD - Dipartimento di Scienze Cliniche e di Comunita, Universita degli Studi di Milano, 20122 Milano, Italy. giulio.pompilio@ccfm.it. FAU - Pramstaller, Peter P AU - Pramstaller PP AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). peter.pramstaller@eurac.edu. FAU - Domingues, Francisco S AU - Domingues FS AUID- ORCID: 0000-0003-4567-4562 AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). francisco.domingues@eurac.edu. FAU - Stilli, Donatella AU - Stilli D AD - Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy. donatella.stilli@unipr.it. FAU - Rossini, Alessandra AU - Rossini A AUID- ORCID: 0000-0002-0440-1130 AD - Institute for Biomedicine, Eurac Research, 39100 Bolzano, Italy (affiliated institute of the University of Lubeck, 23562 Lubeck, Germany). alessandra.rossini@eurac.edu. LA - eng PT - Journal Article DEP - 20180131 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Hydroxamic Acids) RN - 58IFB293JI (Vorinostat) RN - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases) SB - IM MH - Acetylation MH - Animals MH - Histone Deacetylase Inhibitors/pharmacology MH - Humans MH - Hydroxamic Acids/*pharmacology MH - Male MH - Myocytes, Cardiac/*drug effects/enzymology/metabolism MH - *Protein Processing, Post-Translational MH - Rats MH - Rats, Wistar MH - Sarcoplasmic Reticulum Calcium-Transporting ATPases/*metabolism MH - Vorinostat PMC - PMC5855641 OTO - NOTNLM OT - ATPase activity OT - HDAC inhibition OT - SERCA2 OT - acetylation OT - calcium transients OT - cardiomyocyte mechanics COIS- The authors declare no conflict of interest. EDAT- 2018/02/01 06:00 MHDA- 2018/09/08 06:00 PMCR- 2018/02/01 CRDT- 2018/02/01 06:00 PHST- 2017/12/14 00:00 [received] PHST- 2018/01/23 00:00 [revised] PHST- 2018/01/29 00:00 [accepted] PHST- 2018/02/01 06:00 [entrez] PHST- 2018/02/01 06:00 [pubmed] PHST- 2018/09/08 06:00 [medline] PHST- 2018/02/01 00:00 [pmc-release] AID - ijms19020419 [pii] AID - ijms-19-00419 [pii] AID - 10.3390/ijms19020419 [doi] PST - epublish SO - Int J Mol Sci. 2018 Jan 31;19(2):419. doi: 10.3390/ijms19020419.