Defective Ca2+ handling proteins regulation during heart failure

Title:

Defective Ca2+ handling proteins regulation during heart failure

Creator:

Hu, S.-T., Liu, G.-S., Shen, Y.-F., Wang, Y.-L., Tang, Y., and Yang, Y.-J.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:3f11c6b0-f828-4980-9625-d8d696be1a53
uuid:3f11c6b0-f828-4980-9625-d8d696be1a53

Subject:

Fyziologie člověka a srovnávací fyziologie, srdeční selhání, heart failure, sarcoplasmic reticulum, ryanodine receptor, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print

Description:

Abnormal release of Ca2+ from sarcoplasmic reticulum (SR) via the cardiac ryanodine receptor (RyR2) may contribute to contractile dysfunction in heart failure (HF). We previously demonstrated that RyR2 macromol ecular complexes from HF rat were significantly more depleted of FK506 binding protein (FKBP12.6). Here we assess ed expression of key Ca2+ handling proteins and measured SR Ca2+ content in control and HF rat myocytes. Direct measurements of SR Ca2+ content in permeabilized cardiac myocytes demonstrated that SR luminal [Ca2+] is markedly lowered in HF (HF: Δ F / F 0 = 26.4±1.8, n =12; control: Δ F / F 0 = 49.2±2.9, n =10; P <0.01). Furthermore, we demonstrated that the expression of RyR2 associated proteins (including calmodulin, sorcin, calsequestrin, protein phosphatase 1, protein phosphatase 2A), Ca2+ ATPase (SERCA2a), PLB phosphorylation at Ser16 (PLB-S16), PLB phosphorylation at Thr17 (PLB-T17), L-type Ca 2+ channel (Cav1.2) and Na+-Ca 2+ exchanger (NCX) were significantl y reduced in rat HF. Our results suggest that systolic SR reduced Ca2+ release and diastolic SR Ca2+ leak (due to defective protein-protein interaction between RyR2 and its associated proteins) along with reduced SR Ca2+ uptake (due to down-regulation of SERCA2a, PLB-S16 and PLB- T17), abnormal Ca2+ extrusion (due to down-regulation of NCX) and defective Ca2+-induced Ca2+ release (due to down-regulation of Cav1.2) could co ntribute to HF., S.-T. Hu., and Obsahuje bibliografii a bibliografické odkazy

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2011 Volume:60 | Number:1

Harvested from:

CDK

Metadata only:

false