Free Radicals in the Physiological Control of Cell Function

Wulf Dröge

doi:10.1152/physrev.00018.2001

journal article Jan 01, 2002

Free Radicals in the Physiological Control of Cell Function

Wulf Dröge

Physiological Reviews Vol. 82 No. 1 pp. 47-95 · American Physiological Society

View at Publisher Save 10.1152/physrev.00018.2001

Abstract

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, however, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and reestablish “redox homeostasis.” Higher organisms, however, have evolved the use of NO and ROS also as signaling molecules for other physiological functions. These include regulation of vascular tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given signaling protein, oxidative attack induces either a loss of function, a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least in part, from radical-mediated oxidative damage was proposed more than 40 years ago by Harman ( J Gerontol 11: 298–300, 1956). There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.

Topics

No keywords indexed for this article. Browse by subject →

References

647

[1]

10.1126/science.2118682

[2]

10.1074/jbc.271.28.16586

[3]

10.1074/jbc.274.30.21003

[4]

10.1074/jbc.272.33.20389

[5]

10.1038/353668a0

[6]

10.1074/jbc.270.39.22997

[7]

10.1016/0034-5687(94)90043-4

[8]

10.1016/0014-5793(89)81721-1

[9]

Acker H NIPS (1995)

[10]

10.1126/science.274.5294.1917

[11]

10.1073/pnas.94.5.1686

[12]

10.1093/emboj/18.5.1321

[13]

10.1038/sj.onc.1203128

[14]

10.1172/jci119709

[15]

10.1074/jbc.274.36.25821

[16]

10.1074/jbc.270.20.11977

[17]

10.1096/fasebj.8.8.8181668

[18]

10.1023/a:1005904704618

[19]

10.1161/01.hyp.25.2.155

[20]

10.1016/s0891-5849(99)00242-7

[21]

10.1016/s0092-8674(00)81405-1

[22]

10.1073/pnas.90.17.7915

[23]

Angel P Biochim Biophys Acta (1991)

[24]

10.1203/00006450-198701000-00019

[25]

10.1016/s0006-2952(00)00327-0

[26]

10.1002/biof.5520080126

[27]

10.1073/pnas.91.16.7583

[28]

10.1073/pnas.96.11.6161

[29]

Auch-Schwelk W J Cardiovasc Pharmacol (1992) 10.1097/00005344-199200209-00012

[30]

10.1016/s0092-8674(88)91153-1

[31]

10.1016/s0092-8674(88)91153-1

[32]

10.1007/bf01186993

[33]

Axline SG Semin Hematol (1970)

[34]

10.1093/ajcn/62.6.1337s

[35]

10.1161/01.res.77.1.29

[36]

10.1074/jbc.272.1.217

[37]

10.1074/jbc.275.14.10527

[38]

10.1016/s0092-8674(00)81318-5

[39]

Function and Activation of NF-kappaB in the Immune System

P A Baeuerle, T Henkel

Annual Review of Immunology 10.1146/annurev.iy.12.040194.001041

[40]

10.1152/ajpendo.1990.258.6.e957

[41]

Banki K J Immunol (1999) 10.4049/jimmunol.162.3.1466

[42]

10.1038/nsb1295-1043

[43]

10.1074/jbc.274.49.34543

[44]

10.1021/bi990240v

[45]

Mechanisms for Redox Control of Gene Expression

Carl E. Bauer, Sylvie Elsen, Terry H. Bird

Annual Review of Microbiology 10.1146/annurev.micro.53.1.495

[46]

Bauss F Infect Immun (1987) 10.1128/iai.55.7.1622-1625.1987

[47]

10.2337/diab.40.4.405

[48]

10.1073/pnas.85.14.5112

[49]

10.1152/physrev.1998.78.2.547

[50]

10.1126/science.274.5288.782

Showing 50 of 647 references

Cited By

7,434

Understanding the Relationship Between Rhizocephalans and Their Hosts From the Lens of Omics: Implications Towards Crustacean Aquaculture

Yang Yu, Youji Wang · 2026

Reviews in Aquaculture

Docosahexaenoic Acid Modulates Autophagy and Confers Neuronal Resilience under Hypoxia–Reoxygenation Stress

Francis Zamora, Manuel L. Montero · 2026

Journal of Molecular Neuroscience

An ultrasensitive fluorescent strategy based on ligation-promoted exponential amplification for site-specific quantification of 8-oxo-7,8-dihydroguanine in tissues

Fan Huang, Qianqian Du · 2026

Spectrochimica Acta Part A: Molecul...

Electron magnetic resonance imaging: A technical perspective

Eric Weber, Ted Nowak · 2026

Journal of Magnetic Resonance

Antioxidants and Exercise: A Redox-Informed Framework for Training Adaptation, Performance, and Recovery

Dan Cristian Mănescu, Andrei Tudor · 2026

Antioxidants

Fe3+ Reducing Power as the Most Common Assay for Understanding the Biological Functions of Antioxidants

İlhami Gulçin, Saleh H. Alwasel · 2025

Processes

Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond

Noah Sendtner, Rebecca Seitz · 2025

International Journal of Molecular...

Mitophagy and oxidative stress in chronic kidney disease (Review)

Quwu Mushuo, YiHuai Tian · 2025

Molecular Medicine Reports

Regulation of oxidative stress and inflammation caused by drug accumulation in the TME based on EPR-passive strategy and active targeting

Xiang Deng, Zhongsong Zhang · 2025

Cancer Nanotechnology

Preparation, purification and identification of antioxidant peptides from the placenta of Tibetan sheep

Haiwei Ren, Tianzhuo Qin · 2025

Food Bioscience

Associations Between Diabetes Mellitus and Neurodegenerative Diseases

Leszek Szablewski · 2025

International Journal of Molecular...

Integrated multi-omics analysis reveals an interplay of hormonal regulation, antioxidant defense, and lipid signaling during artificial seed aging in Momordica charantia

Yodying Yingchutrakul, Jakkaphan Kumsab · 2025

Plant Physiology and Biochemistry

Potential Role of Oxidative Stress in the Pathophysiology of Neurodegenerative Disorders

Sonia Singh, Ashima Ahuja · 2024

Combinatorial Chemistry & High...

Hypertension, Neurodegeneration, and Cognitive Decline

Anthony Pacholko, Costantino Iadecola · 2024

Hypertension

Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production

Lyudmila V. Bel’skaya, Elena I. Dyachenko · 2024

Current Issues in Molecular Biology

The multifaceted role of mitochondria in autism spectrum disorder

Igor Khaliulin, Wajeha Hamoudi · 2024

Molecular Psychiatry

Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target

Monika Martiniakova, Roman Biro · 2024

International Journal of Molecular...

Mitophagy in fibrotic diseases: molecular mechanisms and therapeutic applications

Xinyan Cui, Zekun Zhou · 2024

Frontiers in Physiology

Identification of Key Genes Associated with Polycystic Ovarian Syndrome and Endometrial and Ovarian Cancer through Bioinformatics

Karishma Raulo, Sahar Qazi · 2024

Journal of Human Reproductive Scien...

Targeting Reactive Oxygen Species for Diagnosis of Various Diseases

Moung Young Lee, Donguk Lee · 2024

Journal of Functional Biomaterials

Metrics

7,434

Citations

647

References

Details

Published: Jan 01, 2002
Vol/Issue: 82(1)
Pages: 47-95

Authors

W

Wulf Dröge

Division of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany

Cite This Article

Wulf Dröge (2002). Free Radicals in the Physiological Control of Cell Function. Physiological Reviews, 82(1), 47-95. https://doi.org/10.1152/physrev.00018.2001

Free Radicals in the Physiological Control of Cell Function

You May Also Like