PMID- 35220548 OWN - NLM STAT- MEDLINE DCOM- 20220411 LR - 20220411 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 477 IP - 5 DP - 2022 May TI - Effect of hyperhomocysteinemia on rat cardiac sarcoplasmic reticulum. PG - 1621-1628 LID - 10.1007/s11010-022-04399-z [doi] AB - Increased concentration of plasma homocysteine (Hcy) is an independent risk factor of cardiovascular disease, yet the mechanism by which hyperhomocysteinemia (HHcy) causes cardiac dysfunction is largely unknown. The aim of present study was to investigate the contribution of sarcoplasmic reticulum to impaired cardiac contractile function in HHCy. HHcy-induced by subcutaneous injection of Hcy (0.45 mumol/g of body weight) twice a day for a period of 2 weeks resulted in significant decrease in developed left ventricular pressure and maximum rate of ventricular relaxation. Our results show that abundances of SR Ca(2+)-handling proteins, Ca(2+)-ATPase (SERCA2), calsequestrin and histidine-rich calcium-binding protein are significantly reduced while the content of phospholamban is unchanged. Moreover, we found that increased PLN:SERCA2 ratio results in the inhibition of SERCA2 activity at low free Ca(2+) concentrations. We further discovered that HHcy is not associated with increased oxidative stress in SR. Taken together, these findings suggest that disturbances in SR Ca(2+) handling, caused by altered protein contents but not oxidative damage, may contribute to impaired cardiac contractility in HHcy. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Tatarkova, Zuzana AU - Tatarkova Z AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia. FAU - Bencurova, Maria AU - Bencurova M AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia. FAU - Lehotsky, Jan AU - Lehotsky J AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia. FAU - Racay, Peter AU - Racay P AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia. FAU - Kmetova Sivonova, Monika AU - Kmetova Sivonova M AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia. FAU - Dobrota, Dusan AU - Dobrota D AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia. FAU - Kaplan, Peter AU - Kaplan P AUID- ORCID: 0000-0002-9299-4190 AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01, Martin, Slovakia. peter.kaplan@uniba.sk. LA - eng GR - 1/0004/19/Vedecka Grantova Agentura MSVVaS SR a SAV/ PT - Journal Article DEP - 20220227 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Calcium-Binding Proteins) RN - 0 (Calsequestrin) RN - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/metabolism MH - Calcium-Binding Proteins/metabolism MH - Calsequestrin/metabolism MH - Heart/physiology MH - *Hyperhomocysteinemia/chemically induced MH - Myocardial Contraction MH - Myocardium/metabolism MH - Rats MH - *Sarcoplasmic Reticulum/metabolism MH - Sarcoplasmic Reticulum Calcium-Transporting ATPases OTO - NOTNLM OT - Ca2+-ATPase OT - Heart OT - Homocysteine OT - Protein expression OT - Sarcoplasmic reticulum EDAT- 2022/02/28 06:00 MHDA- 2022/04/12 06:00 CRDT- 2022/02/27 20:38 PHST- 2021/11/30 00:00 [received] PHST- 2022/02/16 00:00 [accepted] PHST- 2022/02/28 06:00 [pubmed] PHST- 2022/04/12 06:00 [medline] PHST- 2022/02/27 20:38 [entrez] AID - 10.1007/s11010-022-04399-z [pii] AID - 10.1007/s11010-022-04399-z [doi] PST - ppublish SO - Mol Cell Biochem. 2022 May;477(5):1621-1628. doi: 10.1007/s11010-022-04399-z. Epub 2022 Feb 27.