Mechanism of phospholamban inhibition of SERCA2a
نویسندگان
چکیده
منابع مشابه
Modulation of cardiac contractility by the phospholamban/SERCA2a regulatome.
Heart disease remains the leading cause of death and disability in the Western world. Current therapies aim at treating the symptoms rather than the subcellular mechanisms, underlying the etiology and pathological remodeling in heart failure. A universal characteristic, contributing to the decreased contractile performance in human and experimental failing hearts, is impaired calcium sequestrat...
متن کاملAn investigation of the mechanism of inhibition of the Ca(2+)-ATPase by phospholamban.
The Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum has been reconstituted with peptides corresponding to the hydrophobic domain of phospholamban (PLB) with or without the three Cys residues replaced by Ala, and with PLB with the three Cys residues replaced by Ala [PLBcys-(1-52)]. Reconstitution with the hydrophobic domain of PLB[PLB(25-52)] was found to decrease the apparent affinity o...
متن کاملHNO enhances SERCA2a activity and cardiomyocyte function by promoting redox-dependent phospholamban oligomerization.
AIMS Nitroxyl (HNO) interacts with thiols to act as a redox-sensitive modulator of protein function. It enhances sarcoplasmic reticular Ca(2+) uptake and myofilament Ca(2+) sensitivity, improving cardiac contractility. This activity has led to clinical testing of HNO donors for heart failure. Here we tested whether HNO alters the inhibitory interaction between phospholamban (PLN) and the sarcop...
متن کاملSERCA2a superinhibition by human phospholamban triggers electrical and structural remodeling in mouse hearts.
Phospholamban (PLN), the reversible inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), is a key regulator of myocyte Ca(2+) cycling with a significant role in heart failure. We previously showed that the single amino acid difference between human and mouse PLN results in increased inhibition of Ca(2+) cycling and cardiac remodeling and attenuated stress responses in transgen...
متن کاملMechanism-Based Studies of the Active Site-Directed Inhibition and Activation of Enzyme Transketolase
Derivatives of phenyl-keto butenoic acids have been reported to be inhibitors of pyruvate decarboxylase, (PDC). The inhibition of transketolase, a thiamine requiring enzyme such as PDF, by meta nitrophenyl derivative of 2-oxo-3-butenoic acid (MNPB) is reported here. These studies indicate that the inhibitor binds to the enzyme at the active site. A two-step inhibition was observed, first th...
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ژورنال
عنوان ژورنال: Japanese Journal of Pharmacology
سال: 1999
ISSN: 0021-5198
DOI: 10.1016/s0021-5198(19)34419-1