H2O2 alters rat cardiac sarcomere function and protein phosphorylation through redox signaling.
Am J Physiol Heart Circ Physiol
; 299(3): H723-30, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20562337
ABSTRACT
ROS, such as H(2)O(2), are a component of pathological conditions in many organ systems and have been reported to be elevated in cardiac pathophysiology. The experiments presented here test the hypothesis that H(2)O(2) induces alterations in cardiac myofilament function by the posttranslational modification of sarcomeric proteins indirectly through PKC signaling. In vitro assessment of actomyosin Mg(2+)-ATPase activity of myofibrillar fractions showed blunted relative ATP consumption in the relaxed state (pCa 8.0) in response to treatment with 0.5 mM H(2)O(2) before myofilament isolation. The effect was attributable to downstream "redox signaling," inasmuch as the direct application of H(2)O(2) to isolated myofibrils did not alter Mg(2+)-ATPase activity. Ca(2+)-ATPase activity, which was used as a measure of myofibrillar myosin function, was unaffected by H(2)O(2). Functional experiments using rat cardiac trabeculae treated with 0.5 or 5 mM H(2)O(2) followed by detergent extraction of membranes demonstrated increased Ca(2+) sensitivity of force production, a faster rate of force redevelopment, and (for 5 mM) decreased maximum tension. Biochemical analysis of myocardial samples treated with 0.5 mM H(2)O(2) demonstrated increased phosphorylation of two sarcomeric proteins cardiac troponin I and myosin-binding protein-C. These changes were eliminated by a general PKC inhibitor. However, H(2)O(2) and the general PKC activator PMA induced different phosphorylation patterns in cardiomyocytes in which PKC-delta was elevated by viral infection. These data provide evidence that PKC-dependent redox signaling affects the function of cardiac myofilaments and indicate modification of specific proteins through this signaling mechanism.
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Base de dados:
MEDLINE
Assunto principal:
Oxirredução
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Fosforilação
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Sarcômeros
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Miócitos Cardíacos
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Peróxido de Hidrogênio
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article