Oxidation of cardiac myofilament proteins: Priming for dysfunction?

TY - JOUR

T1 - Oxidation of cardiac myofilament proteins: Priming for dysfunction?

AU - Cuello, Friederike

AU - Wittig, Ilka

AU - Lorenz, Kristina

AU - Eaton, Philip

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018/10

Y1 - 2018/10

N2 - Oxidants are produced endogenously and can react with and thereby post-translationally modify target proteins. They have been implicated in the redox regulation of signal transduction pathways conferring protection, but also in mediating oxidative stress and causing damage. The difference is that in scenarios of injury the amount of oxidants generated is higher and/or the duration of oxidant exposure sustained. In the cardiovascular system, oxidants are important for blood pressure homeostasis, for unperturbed cardiac function and also contribute to the observed protection during ischemic preconditioning. In contrast, oxidative stress accompanies all major cardiovascular pathologies and has been attributed to mediate contractile dysfunction in part by inducing oxidative modifications in myofilament proteins. However, the proportion to which oxidative modifications of contractile proteins are beneficial or causatively mediate disease progression needs to be carefully reconsidered. These antithetical aspects will be discussed in this review with special focus on direct oxidative post-translational modifications of myofilament proteins that have been described to occur in vivo and to regulate actin-myosin interactions in the cardiac myocyte sarcomere, the methodologies for detection of oxidative post-translational modifications in target proteins and the feasibility of antioxidant therapy strategies as a potential treatment for cardiac disorders.

AB - Oxidants are produced endogenously and can react with and thereby post-translationally modify target proteins. They have been implicated in the redox regulation of signal transduction pathways conferring protection, but also in mediating oxidative stress and causing damage. The difference is that in scenarios of injury the amount of oxidants generated is higher and/or the duration of oxidant exposure sustained. In the cardiovascular system, oxidants are important for blood pressure homeostasis, for unperturbed cardiac function and also contribute to the observed protection during ischemic preconditioning. In contrast, oxidative stress accompanies all major cardiovascular pathologies and has been attributed to mediate contractile dysfunction in part by inducing oxidative modifications in myofilament proteins. However, the proportion to which oxidative modifications of contractile proteins are beneficial or causatively mediate disease progression needs to be carefully reconsidered. These antithetical aspects will be discussed in this review with special focus on direct oxidative post-translational modifications of myofilament proteins that have been described to occur in vivo and to regulate actin-myosin interactions in the cardiac myocyte sarcomere, the methodologies for detection of oxidative post-translational modifications in target proteins and the feasibility of antioxidant therapy strategies as a potential treatment for cardiac disorders.

KW - Journal Article

KW - Review

U2 - 10.1016/j.mam.2018.08.003

DO - 10.1016/j.mam.2018.08.003

M3 - SCORING: Review article

C2 - 30130564

VL - 63

SP - 47

EP - 58

JO - MOL ASPECTS MED

JF - MOL ASPECTS MED

SN - 0098-2997

IS - SI

ER -