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The role of glycine in regulated cell death

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Abstract

The cytoprotective effects of glycine against cell death have been recognized for over 28 years. They are expressed in multiple cell types and injury settings that lead to necrosis, but are still not widely appreciated or considered in the conceptualization of cell death pathways. In this paper, we review the available data on the expression of this phenomenon, its relationship to major pathophysiologic pathways that lead to cell death and immunomodulatory effects, the hypothesis that it involves suppression by glycine of the development of a hydrophilic death channel of molecular dimensions in the plasma membrane, and evidence for its impact on disease processes in vivo.

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Abbreviations

CCCP:

carbonylcyanide m-chlorophenylhydrazone

COP:

Cytolytic oncotic pore

∆ ψ m :

Mitochondrial membrane potential

EthBr:

Ethidium bromide

LDH:

Lactate dehydrogenase

MPT:

Mitochondrial permeability transition

NHE:

Sodium-hydrogen exchanger

P2X7R:

P2X7 purinergic receptor

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Acknowledgments

Preparation of this manuscript was supported by Merit Review # I01 BX002367 (JMW) from the United States (US) Department of Veterans Affairs. Original investigations by the authors cited here were supported by NIH Grants, DK-34275 (JMW), DK-37139, and DK-48417 (MAV), the Office of Naval Research (JMW), the Department of Veterans Affairs (JMW), and the Dr. Werner Jackstaedt-Foundation (AB). The contents do not represent the views of the US Department of Veterans Affairs or the United States Government.

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Veterans Affairs Ann Arbor Healthcare System and University of Michigan, Room 1560, MSRB II, Ann Arbor, MI, 48109-0676, USA

    Joel M. Weinberg

  2. Department of Nephrology, University Duisburg-Essen, 45122, Essen, Germany

    Anja Bienholz

  3. Department of Pathology, University of Texas Health Science Center, San Antonio, TX, 78234, USA

    M. A. Venkatachalam

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  1. Joel M. Weinberg
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  3. M. A. Venkatachalam
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Weinberg, J.M., Bienholz, A. & Venkatachalam, M.A. The role of glycine in regulated cell death. Cell. Mol. Life Sci. 73, 2285–2308 (2016). https://doi.org/10.1007/s00018-016-2201-6

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