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The Significance of NO-Synthase, Reactive Oxygen Species, Kinases and KATP-Channels in the Development of the Infarct-Limiting Effect of Adaptation to Hypoxia

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Abstract

The cardioprotective effect of chronic hypoxia (CH) is associated with the activation of inducible nitric oxide synthase (iNOS). Reactive oxygen species (ROS) are involved in the development of CH-induced cardiac tolerance to ischemia/reperfusion. The infarct-limiting effect of CH depends on the opening of mitochondrial ATP-sensitive potassium (mitoKATP) channels. Protein kinase C δ and ε isoforms are involved in the cardioprotective effect of adaptation to hypoxia. CH increases the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), Ca2+/calmodulin-dependent protein kinase II (CaMKII), phosphorylated p38 (p-p38), phosphorylated AMP-activated protein kinase (p-AMPK), as well as hexokinase-1 (HK1) and hexokinase-2 (HK2). ERK1/2 and mitogen-activated protein kinases (MEK1/2) are involved in the cardioprotective effect of adaptation to hypoxia. The role of atrial natriuretic peptide (ANP), erythropoietin, endothelin-1, phosphoinositide 3-kinases (PI3K), protein kinase G (PKG), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) in the protective effect of adaptation to hypoxia requires further research.

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Funding

This work was supported by the Russian Foundation for Basic Research (RFBR), grant no. 21-515-53003. The role of ERK1/2 in the infarct-limiting effect of chronic hypoxia was evaluated within the state assignment (122020300042-4).

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Authors and Affiliations

  1. Cardiology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia

    N. V. Naryzhnaya, L. N. Maslov & I. A. Derkachev

  2. Fourth Military Medical University (FMMU), Xi’an, China

    F. Fu

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  1. N. V. Naryzhnaya
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  2. L. N. Maslov
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  3. I. A. Derkachev
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  4. F. Fu
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Contributions

Conceptualization and design (N.V.N.); reviewing of published data (L.N.M., I.A.D.); writing and editing a manuscript (I.A.D.); selection of information sources (F. Fu).

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Correspondence to N. V. Naryzhnaya.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 4, pp. 414–439https://doi.org/10.31857/S0869813922040069.

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Naryzhnaya, N.V., Maslov, L.N., Derkachev, I.A. et al. The Significance of NO-Synthase, Reactive Oxygen Species, Kinases and KATP-Channels in the Development of the Infarct-Limiting Effect of Adaptation to Hypoxia. J Evol Biochem Phys 58, 535–547 (2022). https://doi.org/10.1134/S0022093022020211

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