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Intracellular redox status and oxidative stress: implications for cell proliferation, apoptosis, and carcinogenesis

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Abstract

Oxidative stress can be defined as the imbalance between cellular oxidant species production and antioxidant capability. Reactive oxygen species (ROS) are involved in a variety of different cellular processes ranging from apoptosis and necrosis to cell proliferation and carcinogenesis. In fact, molecular events, such as induction of cell proliferation, decreased apoptosis, and oxidative DNA damage have been proposed to be critically involved in carcinogenesis. Carcinogenicity and aging are characterized by a set of complex endpoints, which appear as a series of molecular reactions. ROS can modify many intracellular signaling pathways including protein phosphatases, protein kinases, and transcription factors, suggesting that the majority of the effects of ROS are through their actions on signaling pathways rather than via non-specific damage of macromolecules; however, exact mechanisms by which redox status induces cells to proliferate or to die, and how oxidative stress can lead to processes evoking tumor formation are still under investigation.

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Abbreviations

AP-1:

Activating protein-1

ASK1:

Apoptosis signal-regulating kinase 1

CDK:

Cyclin-dependent kinase

C/EBP:

CAAT/enhancer-binding protein

COX-2:

Cyclooxygenase-2

DDR:

DNA damage response

DHMC:

7,8-Dihydroxy-4-methylcoumarin

DISC:

Death-inducing signaling complex

DMBA:

7,12-Dimethylbenz[a]anthracene

ERK:

Extracellular signal-regulated kinase

FAA:

Flavone acetic acid

FADD:

Fas-associated death domain protein

Fe-NTA:

Ferric nitrilotriacetate

GA:

Glutaminase

GABA:

Gamma-aminobutyric acid

GSH:

Glutathione

GSSG:

Oxidized glutathione

GST:

Glutathione S-transferase

GTP:

Guanosine-5′-triphosphate

HSP:

Heat shock protein

IGF:

Insuline-like growth factor

IL:

Interleukine

JNK:

c-Jun NH2-terminal kinase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MDM:

Murine double minute

MKP-1:

MAPK phosphatase-1

MT:

Metallothioneins

NAC:

N-acetyl-l-cysteine

NADPH:

Reduced nicotinamide-adenine dinucleotide phosphate

NFAT:

Nuclear factor of activated T cells

NFκB:

Necrosis factor kappa B

NO:

Nitric oxide

NOS:

Nitric oxide synthase

PARP:

Poly(ADP-ribose) polymerase

PCNA:

Proliferating cell nuclear antigen

PD:

Parkinson’s disease

PI3-K:

Phosphatidylinositol 3-kinase

PK:

Protein kinase

POX:

Proline oxidase

RNS:

Reactive nitrogen species

ROK:

Rho kinase

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TAK-1:

Transforming growth factor-beta-activated kinase-1

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

TRAIL:

Tumor necrosis factor-alpha-related apoptosis-inducing ligand

UCP2:

Uncoupling protein-2

8-OHdG:

8-Hydroxy-2′-deoxyguanosine

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Acknowledgments

We thank the Ministerio de Ciencia y Tecnología of Spain, SAF2004-02339, and Junta de Andalucía, Proyectos de Investigación de Excelencia, Convocatoria 2006, CVI-01543, Spain.

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  1. Department of Biología Molecular y Bioquímica, Facultad de Ciencias, Campus de Teatinos, Universidad de Málaga, 29071, Málaga, Spain

    José M. Matés, Juan A. Segura, Francisco J. Alonso & Javier Márquez

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  1. José M. Matés
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Matés, J.M., Segura, J.A., Alonso, F.J. et al. Intracellular redox status and oxidative stress: implications for cell proliferation, apoptosis, and carcinogenesis. Arch Toxicol 82, 273–299 (2008). https://doi.org/10.1007/s00204-008-0304-z

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