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Role of glutathione, glutathione transferase, and glutaredoxin in regulation of redox-dependent processes

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Abstract

Over the last decade fundamentally new features have been revealed for the participation of glutathione and glutathione-dependent enzymes (glutathione transferase and glutaredoxin) in cell proliferation, apoptosis, protein folding, and cell signaling. Reduced glutathione (GSH) plays an important role in maintaining cellular redox status by participating in thiol-disulfide exchange, which regulates a number of cell functions including gene expression and the activity of individual enzymes and enzyme systems. Maintaining optimum GSH/GSSG ratio is essential to cell viability. Decrease in the ratio can serve as an indicator of damage to the cell redox status and of changes in redox-dependent gene regulation. Disturbance of intracellular GSH balance is observed in a number of pathologies including cancer. Consequences of inappropriate GSH/GSSG ratio include significant changes in the mechanism of cellular redox-dependent signaling controlled both nonenzymatically and enzymatically with the participation of isoforms of glutathione transferase and glutaredoxin. This review summarizes recent data on the role of glutathione, glutathione transferase, and glutaredoxin in the regulation of cellular redox-dependent processes.

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Abbreviations

AIF:

apoptosis-inducing factor

AMPK:

serine/threonine AMP-activated protein kinase

ARE:

antioxidant responsive element

ASK1:

apoptosis signal-regulating kinase-1

BSO:

buthionine sulfoximine

ERK:

extracellular signal-regulated kinase

γ-GCL:

γ-glutamylcysteine ligase

GPx:

glutathione peroxidase

Grx:

glutaredoxin

GS:

glutathione synthetase

GSH/GSSG:

glutathione reduced/oxidized

GST:

glutathione S-transferase

γ-GT:

γ-glutamyltransferase

JNK:

c-Jun N-terminal kinase

LPO:

lipid peroxidation

MAPK:

mitogen-activated protein kinase

mGSH:

mitochondrial glutathione

nGSH:

nuclear glutathione

OGC:

2-oxyglutarate carrier

PARP:

poly(ADP-ribose)polymerase

Prx:

peroxiredoxin

RNS:

reactive nitrogen species

ROS:

reactive oxygen species

Trx:

thioredoxin

TrxR:

thioredoxin reductase

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Authors and Affiliations

  1. Peoples’ Friendship University of Russia, ul. Miklukho-Maklaya 6, 117198, Moscow, Russia

    E. V. Kalinina, N. N. Chernov & M. D. Novichkova

Authors
  1. E. V. Kalinina
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  2. N. N. Chernov
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  3. M. D. Novichkova
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Correspondence to E. V. Kalinina.

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Original Russian Text © E. V. Kalinina, N. N. Chernov, M. D. Novichkova, 2014, published in Uspekhi Biologicheskoi Khimii, 2014, Vol. 54, pp. 299–348.

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Kalinina, E.V., Chernov, N.N. & Novichkova, M.D. Role of glutathione, glutathione transferase, and glutaredoxin in regulation of redox-dependent processes. Biochemistry Moscow 79, 1562–1583 (2014). https://doi.org/10.1134/S0006297914130082

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  • DOI: https://doi.org/10.1134/S0006297914130082

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