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β-Arrestin prevents cell apoptosis through pro-apoptotic ERK1/2 and p38 MAPKs and anti-apoptotic Akt pathways

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Abstract

Our previous studies have shown that β-arrestin 2 plays an anti-apoptotic effect. However, the mechanisms by which β-arrestin contribute to anti-apoptotic role remain unclear. In this study, we show that a deficiency of either β-arrestin 1 or β-arrestin 2 significantly increases serum deprivation (SD)-induced percentage of apoptotic cells. β-arrestin 2 deficient-induced apoptosis was inhibited by transfection with β-arrestin 2 full-length plasmid, revealing that SD-induced apoptosis is dependent on β-arrestin 2. Furthermore, in the absence of either β-arrestin 1 or β-arrestin 2 significantly enhances SD-induced the level of pro-apoptotic proteins, including cleaved caspase-3, extracellular-signal regulated kinase 1/2 (ERK1/2) and p38, members of mitogen-activated protein kinases (MAPKs). In addition, a deficiency of either β-arrestin 1 or β-arrestin 2 inhibits phosphorylation of Akt. The SD-induced changes in cleaved caspase-3, ERK1/2 and p38 MAPKs, Akt, and apoptotic cell numbers could be blocked by double knockout of β-arrestin 1/2. Our study thus demonstrates that β-arrestin inhibits cell apoptosis through pro-apoptotic ERK1/2 and p38 MAPKs and anti-apoptotic Akt signaling pathways.

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Abbreviations

KO:

Knockout

DKO:

Double knockout

SD:

Serum deprivation

TUNEL:

Terminal deoxynucleotidyl transferase biotin dUTP nick end labeling

ERK1/2:

Extracellular-signal regulated kinase 1/2

MAPKs:

Mitogen-activated protein kinases

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Acknowledgments

This work was supported in part by Shanghai Technology Department to Q. Li. The authors wish to express their appreciation to Dr. Robert Lefkowitz, Duke University Medical School, for providing WT MEFs, β-arrestin 1 or 2 KO MEFs, and β-arrestin 1/2 DKO MEFs and to Dr. Gang Pei, Shanghai Institutes for Biological Science of China, for providing β-arrestin 2 full-length plasmid and control plasmid.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China

    Xiaohua Yang & Haixin Qian

  2. Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA

    Xiaohua Yang, Hui Li & Deling Yin

  3. Department of Pathology, Shandong University School of Medicine, Jinan, 250012, China

    Gengyin Zhou

  4. Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China

    Tao Ren & Qinchuan Li

  5. Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, China

    Yanjun Zhang

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  1. Xiaohua Yang
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Correspondence to Haixin Qian or Qinchuan Li.

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Yang, X., Zhou, G., Ren, T. et al. β-Arrestin prevents cell apoptosis through pro-apoptotic ERK1/2 and p38 MAPKs and anti-apoptotic Akt pathways. Apoptosis 17, 1019–1026 (2012). https://doi.org/10.1007/s10495-012-0741-2

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