AIMS: β-adrenergic augmentation of Ca2+ sparks and cardiac contractility has been functionally linked to phosphorylation-dependent dissociation of FK506 binding protein 12.
Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ handling in heart failure（HF） model of rats and to explore the underlying molecular mechanisms. Methods：HF ...Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ handling in heart failure（HF） model of rats and to explore the underlying molecular mechanisms. Methods：HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham（n=10）, model（n=10）, QSG（n=12, 2.2 g/kg daily） and metoprolol groups（n=12, 10.5 mg/kg daily）. The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca^2＋ concentration and sarco-endoplasmic reticulum ATPase 2a（SERCA2a） activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2＋ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. Results：HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca^2＋ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2＋ level. QSG prevented defective Ca^2＋ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca^2＋ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion：QSG restored SR Ca^2＋cycling in HF rats and served as an ideal alternative drug for treating HF.展开更多
Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition,...Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.展开更多
文摘AIMS: β-adrenergic augmentation of Ca2+ sparks and cardiac contractility has been functionally linked to phosphorylation-dependent dissociation of FK506 binding protein 12.
基金Supported by the National Natural Science Foundation of China(No.81530100,81470191,and 81302908)
文摘Objective：To assess the effects of Qishen Granule（芪参颗粒, QSG） on sarcoplasmic reticulum（SR） Ca^2＋ handling in heart failure（HF） model of rats and to explore the underlying molecular mechanisms. Methods：HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham（n=10）, model（n=10）, QSG（n=12, 2.2 g/kg daily） and metoprolol groups（n=12, 10.5 mg/kg daily）. The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca^2＋ concentration and sarco-endoplasmic reticulum ATPase 2a（SERCA2a） activity were detected by specific assay kits. Expressions of the critical regulators in SR Ca^2＋ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. Results：HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca^2＋ releaseuptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca^2＋ level. QSG prevented defective Ca^2＋ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca^2＋ uptake by up-regulating expression and activity of SERCA2 a and promoting phosphorylation of phospholamban. Conclusion：QSG restored SR Ca^2＋cycling in HF rats and served as an ideal alternative drug for treating HF.
基金supported over the past couple of years by the Deutsche Forschungsge-meinschaftthe Gemeinnützige Hertie-Stiftung+1 种基金the Well-come Trustthe Deutsche Akademische Austauschdienst
文摘Cyclic ADP-ribose (cADPR) is a universal Ca2+ mobilizing second messenger in many different cell types and organisms. cADPR activates Ca2+ release from endo/sarcoplasmic reticulum via ryanodine receptors. In addition, Ca2+ entry secondary to Ca2+ depletion is at least one of the mechanisms in which cADPR triggers Ca2+ inflow, too. Analogues of cADPR have been prepared by chemical and chemo-enzymatic routes. Most of the analogues were analyzed for biological activity in intact or permeabilized Jurkat T cells (a human T-lymphoma cell line). As a systematic approach, analogues were grouped according to alterations in the base, the northern ribose, the southern ribose, the pyrophosphate backbone, or in complex modifications, comprising more than one part of the molecule. Biological activity of the analogues is reviewed, with special emphasis on Jurkat T cells.
