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Negligible effect of eNOS palmitoylation on fatty acid regulation of contraction in ventricular myocytes from healthy and hypertensive rats

  • Muscle Physiology
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Abstract

S-palmitoylation is an important post-translational modification that affects the translocation and the activity of target proteins in a variety of cell types including cardiomyocytes. Since endothelial nitric oxide synthase (eNOS) is known to be palmitoylated and the activity of eNOS is essential in fatty acid-dependent β-oxidation in muscle, we aimed to test whether palmitoylation of eNOS is involved in palmitic acid (PA) regulation of left ventricular (LV) myocyte contraction from healthy (sham) and hypertensive (HTN) rats. Our results showed that PA, a predominant metabolic substrate for cardiac β-oxidation, significantly increased contraction and oxygen consumption rate (OCR) in LV myocytes from sham. Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) or eNOS gene deletion prevented PA regulation of the myocyte contraction or OCR, indicating the pivotal role of eNOS in mediating the effects of PA in cardiac myocytes. PA increased the palmitoylation of eNOS in LV myocytes and depalmitoylation with 2-bromopalmitate (2BP; 100 μM) abolished the increment. Furthermore, although PA did not increase eNOS-Ser1177, 2BP reduced eNOS-Ser1177 with and without PA. Intriguingly, PA-induced increases in contraction and OCR were unaffected by 2BP treatment. In HTN, PA did not affect eNOS palmitoylation, eNOS-Ser1177, or myocyte contraction. However, 2BP diminished eNOS palmitoylation and eNOS-Ser1177 in the presence and absence of PA but did not change myocyte contraction. Collectively, our results confirm eNOS palmitoylation in LV myocytes from sham and HTN rats and its upregulation by PA in sham. However, such post-transcriptional modification plays negligible role in PA regulation of myocyte contraction and mitochondrial activity in sham and HTN.

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Authors and Affiliations

  1. Department of Physiology and Biomedical Sciences, Ischemic/hypoxic Disease Institute, Seoul National University, College of Medicine, Jongno Gu, 103 Dae Hak Ro, Seoul, 110-799, South Korea

    Chun Li Jin, Yu Na Wu, Ji Hyun Jang, Zai Hao Zhao, Sung Joon Kim & Yin Hua Zhang

  2. Yan Bian University Hospital, Yanji, Ji Lin, China

    Chun Li Jin & Yin Hua Zhang

  3. Department of Life Sciences, Ewha Woman’s University, Seoul, South Korea

    Goo Taeg Oh

  4. Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    Yin Hua Zhang

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  1. Chun Li Jin
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  2. Yu Na Wu
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  3. Ji Hyun Jang
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Correspondence to Yin Hua Zhang.

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The authors declare that they have no conflicts of interest.

Sources of funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013068067); by the Brain Korea 21 Graduate Programme of the Korean Ministry of Education, Science and Technology; Seoul National University Hospital; the Korean Society of Hypertension (2013); SK Telecom Research Fund (no. 3420130290); and from the National Natural Science Foundation of China (NSFC; 31460265).

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Jin, C.L., Wu, Y.N., Jang, J.H. et al. Negligible effect of eNOS palmitoylation on fatty acid regulation of contraction in ventricular myocytes from healthy and hypertensive rats. Pflugers Arch - Eur J Physiol 469, 1141–1149 (2017). https://doi.org/10.1007/s00424-017-1979-x

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  • DOI: https://doi.org/10.1007/s00424-017-1979-x

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