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Eicosapentaenoic acid attenuated oxidative stress-induced cardiomyoblast apoptosis by activating adaptive autophagy

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Abstract

Purpose

Recently, several large, randomized clinical trials have proven the benefits of eicosapentaenoic acid (EPA) in cardiovascular prevention. However, the precise protective mechanisms of EPA for heart disease are still controversial. In this study, we evaluate the possible protective effects of EPA, especially the role of autophagy, against cardiomyocyte apoptosis induced by oxidative stress.

Methods

H9C2 myocardioblasts were incubated with 80 μM EPA for 24 h and then exposed to 400 μM of hydrogen peroxide for 3 h. Autophagic response, lysosome function, and apoptosis were analyzed at the end of the experiment.

Results

Preincubation of EPA significantly inhibited apoptosis and increased cell viability for H9C2 cells under oxidative stress. The effects of EPA on apoptosis and cell viability were suppressed by 3-MA treatment (autophagic inhibitor). Oxidative stress decreased Beclin 1 protein expression, increased the ratio of LC3II/LC3I, and reduced the formation of acid organelles, whereas the preincubation of EPA abrogated the negative effect of oxidative stress on H9C2 by mediating the autophagic response. Inhibiting autophagy by 3-methyladenine reversed the EPA effect significantly by increasing the ratio of LC3II–LC3I. Treatment with 3-MA did not alter the increment of acid organelles by EPA preincubation. In addition, EPA restored the phosphorylation of Akt activated by H2O2 treatment and induced the phosphorylation of AMPK in H9C2 cells under oxidative stress.

Conclusion

EPA attenuated oxidative stress-induced cardiomyocyte apoptosis by activating an adaptive autophagic response.

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Acknowledgments

This work was supported by the Research Grant NSC 98-2314-B-002-121-MY3, NSC 100-2313-B-002-053, NSC 101-2313-B-002-030-MY3 and 10R70615-3. The study was sponsored, conducted, and analyzed by the National Science Council and National Taiwan University. The authors are grateful to Miss Chein Jun Kao for technical assistance.

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Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan S Rd., Taipei, Taiwan

    Hsiu-Ching Hsu & Ming-Fong Chen

  2. Department of Animal Science and Technology, National Taiwan University, 50 Lane 155, Sec. 3, Keelung Rd., Taipei, 106, Taiwan

    Ching-Yi Chen & Chun-Hsien Chiang

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  1. Hsiu-Ching Hsu
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  2. Ching-Yi Chen
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  4. Ming-Fong Chen
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Correspondence to Ching-Yi Chen.

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Hsu, HC., Chen, CY., Chiang, CH. et al. Eicosapentaenoic acid attenuated oxidative stress-induced cardiomyoblast apoptosis by activating adaptive autophagy. Eur J Nutr 53, 541–547 (2014). https://doi.org/10.1007/s00394-013-0562-2

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  • DOI: https://doi.org/10.1007/s00394-013-0562-2

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