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Inhibition of suicidal erythrocyte death by pyrogallol

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Abstract

Pyrogallol, a polyphenolic component of Acacia nilotica has previously been reported to induce apoptosis of diverse cell types. Pyrogallol is in part effective by influencing gene expression and by interference with mitochondrial function. Despite lack of nuclei and mitochondria, erythrocytes may undergo eryptosis, a suicidal death apparent from phosphatidylserine translocation to the erythrocyte surface and cell shrinkage. Eryptosis is triggered by glucose depletion, by oxidation, by hyperosmotic cell shrinkage and by excessive Ca2+ entry. As enhanced eryptosis is a common cause of anemia, uncovering inhibitors and stimulators of eryptosis may, both, be of clinical interest. Here we tested, whether eryptosis of human erythrocytes is modified by pyrogallol. Utilizing flow cytometry, phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding and cell volume from forward scatter. Prior to determinations erythrocytes were incubated with or without glucose, without or with added oxidant tert-butyl-hydroperoxide (t-BOOH, 0.5 mM), without or with added hyperosmotic sucrose (550 mM) or without or with added Ca2+ ionophore ionomycin (1 µM). Treatment of erythrocytes with pyrogallol (2–8 µM) was without significant effect on annexin-V-binding and forward scatter. Glucose deprivation, t-BOOH, sucrose and ionomycin, each, triggered annexin-V-binding and decreased forward scatter. Pyrogallol significantly blunted the effects on annexin-V-binding but not on forward scatter. Pyrogallol thus blunts phosphatidylserine translocation in erythrocytes exposed to glucose depletion, oxidative stress, hyperosmotic shock and excessive Ca2+ entry.

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Acknowledgements

The authors acknowledge the meticulous preparation of the manuscript by Lejla Subasic. Jibin Liu is supported by Chinese Scholarship Council.

Funding

This study was funded by China Agricultural Research System (CARS-42-17), Integration and Demonstration of Key Technologies for Goose Industrial Chain in Sichuan Province (2018NZ0005), Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System (CARS-SVDIP).

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  1. Jibin Liu and Abdulla Al Mamun Bhuyan have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Animal Disease and Human Health of Sichuan Province, Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, 611130, People’s Republic of China

    Jibin Liu, Shaqiu Zhang & Anchun Cheng

  2. Department of Physiology, Eberhard-Karls-University, Wilhelmstr. 56, 72076, Tuebingen, Germany

    Jibin Liu, Abdulla Al Mamun Bhuyan, Ke Ma & Florian Lang

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  1. Jibin Liu
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Contributions

JL, AAMB, AC and FL conceived and designed research. Material preparation, data collection and analysis were performed by JL, AAMB, KM and SZ. The first draft of the manuscript was written by FL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Anchun Cheng or Florian Lang.

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Liu, J., Bhuyan, A.A.M., Ma, K. et al. Inhibition of suicidal erythrocyte death by pyrogallol. Mol Biol Rep 47, 5025–5032 (2020). https://doi.org/10.1007/s11033-020-05568-3

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