Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca²⁺ signaling in ventricular myocytes
Experimental & Molecular Medicine
;
: e341-2017.
Artigo
em Inglês
| WPRIM
| ID: wpr-93424
ABSTRACT
Cyclic ADP-ribose (cADPR) releases Ca²⁺ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca²⁺ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca²⁺ ([Ca²⁺](i)) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca²⁺ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca²⁺ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Retículo
/
Tirosina
/
Potenciais de Ação
/
Difosfato de Adenosina
/
Cálcio
/
Proteínas Tirosina Fosfatases
/
Adenosina Trifosfatases
/
Canal de Liberação de Cálcio do Receptor de Rianodina
/
Citocalasina B
/
Células Musculares
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2017
Tipo de documento:
Artigo
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