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Phosphoinositide 3-kinase accelerates autophagic cell death during glucose deprivation in the rat cardiomyocyte-derived cell line H9c2

Oncogene volume 22, pages 8529–8535 (2003)Cite this article

Abstract

We investigated cell death during glucose deprivation in rat cardiomyocyte-derived H9c2 cells. Electron microscopic analysis revealed accumulation of autophagic vacuoles during glucose deprivation. The addition of 3-methyladenine or LY294002, which are known to inhibit autophagosome formation, reduced cell death while Z-VAD-FMK, a caspase inhibitor, slightly affected cell death. Thus, cell death during glucose deprivation is not type I programmed cell death (apoptotic cell death) but type II programmed cell death (autophagic cell death). Moreover, we found that both insulin-like growth factor-I and the adenovirus-mediated overexpression of wild-type class I PI 3-kinase accelerated cell death as well as accumulation of autophagic vacuoles during glucose deprivation while dominant-negative PI 3-kinase reduced these phenomena. The results indicate that IGF-I/PI 3-kinase accelerates the accumulation of autophagic vacuoles and subsequent autophagic cell death during glucose deprivation, revealing the opposing role of IGF-I/PI 3-kinase in two distinct types of programmed cell death (apoptotic and autophagic cell death).

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Abbreviations

PI:

phosphoinositide

3MA:

3-methyladenine

Z-VAD-FMK:

benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone

IGF:

insulin-like growth factor

LC3:

microtubule-associated protein 1 light chain 3

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Acknowledgements

The authors would like to thank Dr Yoshitomo Oka (Tohoku University) for his kind gift of recombinant adenoviruses of wild-type and dominant-negative PI 3-kinases and Dr Tamotsu Yoshimori (National Institute of Genetics) for providing antibodies against LC3. This work was supported in part by grants from the Ministry of Education, Science and Culture of Japan, Yamanouchi Foundation for Research on Metabolic Disorders, The Inamori Foundation, The Kowa Life Science Foundation, Takeda Science Foundation, The Mochida Memorial Foundation for Medical and Pharmaceutical Research, Japan Heart Foundation Research Grant, NOVARTIS Foundation (Japan) for the Promotion of Science, Research Program for Special Promotion of the Venture Business Laboratory, Yamaguchi University, Osaka Cancer Research Foundation, The Old Age Research Foundation of Yamaguchi, and Yamaguchi Industrial Promotion Foundation (for YM).

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Authors and Affiliations

  1. Center for Gene Research, Yamaguchi University, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan

    Toshihiko Aki & Yoichi Mizukami

  2. Department of Legal Medicine School of Medicine, Yamaguchi University, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan

    Toshihiko Aki & Tatsuya Fujimiya

  3. Institute of Laboratory Animals, Yamaguchi University, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan

    Kazuhito Yamaguchi

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  1. Toshihiko Aki
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Correspondence to Toshihiko Aki.

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Aki, T., Yamaguchi, K., Fujimiya, T. et al. Phosphoinositide 3-kinase accelerates autophagic cell death during glucose deprivation in the rat cardiomyocyte-derived cell line H9c2. Oncogene 22, 8529–8535 (2003). https://doi.org/10.1038/sj.onc.1207197

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