Copper/Zinc Superoxide Dismutase in Human Skin: Current Knowledge
Open accessAbstract
Superoxide dismutase is widespread in the human body, including skin and its appendages. Here, we focus on human skin copper/zinc superoxide dismutase, the enzyme that protects skin and its appendages against reactive oxygen species. Human skin copper/zinc superoxide dismutase resides in the cytoplasm of keratinocytes, where up to 90% of cellular reactive oxygen species is produced. Factors other than cell type, such as gender, age and diseased state influence its location in skin tissues. We review current knowledge of skin copper/zinc superoxide dismutase including recent studies in an attempt to contribute to solving the question of its remaining unexplained functions. The research described here may be applicable to pathologies associated with oxidative stress. However, recent studies on copper/zinc superoxide dismutase in yeast reveal that its predominant function may be in signaling pathways rather than in scavenging superoxide ions. If confirmed in the skin, novel approaches might be developed to unravel the enzyme's remaining mysteries.
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Manganese and copper are involved in antioxidant mechanisms through their structural role within SOD and other enzymes protecting cells from oxidative stress.
“Manganese and copper are further trace elements involved in antioxidant mechanisms through their structural role within SOD and other crucial enzymes useful for protecting cells from OS [447,448,449].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [447]
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“Some reports show the relationship of SOD with the proliferation of epithelial cells which were explored for skin carcinomas (Altobelli et al. 2020).”
BackgroundThe Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
Antioxidants to Defend Healthy and Youthful Skin—Current Trends and Future Directions in Cosmetology
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Therapeutic Applications and Mechanisms of Superoxide Dismutase (SOD) in Different Pathogenesis
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“Important endogenous enzymatic antioxidants include catalase (CAT), glutathione peroxidase (GPx), SOD1 (containing copper and zinc), SOD2 (containing manganese) and extracellular SOD3 (also containing copper and zinc), peroxiredoxins, and thioredoxins [15-18].”
BackgroundShedding a New Light on Skin Aging, Iron- and Redox-Homeostasis and Emerging Natural Antioxidants
Pourzand, C., Albieri, A., & Raczek, N. N. (2022) · Antioxidants · doi:10.3390/antiox11030471 · Cited by 62 · see citing works
The Role of Selected Trace Elements in Oxidoreductive Homeostasis in Patients with Thyroid Diseases
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Zinc Deficiency as a General Feature of Cancer: a Review of the Literature
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“Other studies showed that copper-zinc superoxide dismutase protects tissues from reactive oxygen species, and alterations in the activity of this enzyme have been associated with a wide range of diseases [12, 13].”
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“Copper, alongside zinc, is integral to the functioning of antioxidant enzymes such as SOD-1 and SOD-3 [42,43].”
BackgroundNRF2 and Key Transcriptional Targets in Melanoma Redox Manipulation
Carpenter, E. L., Becker, A. L., & Indra, A. K. (2022) · Cancers · doi:10.3390/cancers14061531 · Cited by 42 · see citing works
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Anti-ageing peptides and proteins for topical applications: a review
Liu, M., Chen, S., Zhang, Z., Li, H., Sun, G., Yin, N., & Wen, J. (2021) · Pharmaceutical Development and Technology · doi:10.1080/10837450.2021.2023569 · Cited by 33 · see citing works
“It is prooxidative as it may reduce transition metals, liberate protein-bound metals, and generate the perhydroxyl radical, and then directly accelerate lipid oxidation under acidic circumstances (pH <4.8) (Elias et al. 2008; Altobelli et al. 2020).”
BackgroundInfluentialMercury transformations in algae, plants, and animals: The occurrence, mechanisms, and gaps
Li, S., Li, Z., Wu, M., Zhou, Y., Tang, W., & Zhong, H. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.168690 · Cited by 30 · see citing works
Rapid self-calibrating fluorescent detection of copper (II) ions in wine with high accuracy
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Nutrición animal: Texto de formación universitaria
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Navigating Transition Metal‐Dependent Cell Death: Mechanisms, Crosstalk, and Future Directions
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Exploring Copper’s role in stroke: progress and treatment approaches
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Mangiferin alleviates hyperglycemia-induced endothelial impairment via Nrf2 signaling pathway
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“SOD3 is a highly conserved enzyme that is widespread in the human body and plays a fundamental role in protecting cells from oxidative stress [22].”
BackgroundRegulation of Mitochondrial Dynamics in Parkinson’s Disease—Is 2-Methoxyestradiol a Missing Piece?
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Metal ion formulations for diabetic wound healing: Mechanisms and therapeutic potential
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Functionalized Silica Star-Shaped Nanoparticles and Human Mesenchymal Stem Cells: An In Vitro Model
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“We monitored the presence of oxidative stress by evaluating the SOD1 expression [66,67].”
Serum Copper Level and Polycystic Ovarian Syndrome: A Meta-Analysis
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Oral delivery of a highly stable superoxide dismutase as a skin aging inhibitor
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Serum Copper and Zinc levels among Iranian vitiligo patients
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The role of trace elements for the function and health of the skin
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Healthy lifestyle choices: new insights into vitiligo management
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Minerals and Trace Elements: Key Protectors of Skin Health and Defenders against Skin Disorders
Bjørklund, G., Shanaida, M., Гонтова, Т. М., Gheorghe, E., Kassym, L., Kussainova, A., Voloshyn, V., Semenova, Y. M., Lysiuk, R., Voloshyn, O., et al. (2025) · Current Medicinal Chemistry · doi:10.2174/0109298673348175250214054101 · Cited by 10 · see citing works
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Enhanced flux potential analysis links changes in enzyme expression to metabolic flux
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“…h 2 O 2 . cat is one of the crucial antioxidant enzymes that strongly mitigates oxidative stress by decomposing cellular h 2 O 2 into water. a deficiency or the malfunction of cat has been implicated in the pathogenesis of many age-associated degenerative diseases (altobelli et al., 2020).”
Post-traumatic stress disorder and metabolic syndrome: the role of some antioxidants in treatment
Serhiyenko, V. A., Oliinyk, A. Y., Pavlovskiy, Y., Kruk, O. S., & Serhiyenko, A. A. (2024) · INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) · doi:10.22141/2224-0721.20.6.2024.1445 · Cited by 6 · see citing works
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“23 Copper deficiency is uncommon; however, it has been reported in preterm neonates, cowmilk-fed infants, and infants recovering from diarrhoea-caused malnutrition.”
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Development and Validation of a Fluorogenic Probe for Lysosomal Zinc Release
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“These mechanisms can be categorized into enzymatic (such as copper-zinc superoxide dismutase and catalase) and non-enzymatic (including glutathione) [10].”
BackgroundKim, M.-B., Park, S.-M., Lim, G., Oh, Y.-H., Seo, K.-W., & Youn, H. (2024) · PLoS ONE · doi:10.1371/journal.pone.0303136 · Cited by 3 · see citing works
“It is generated during many cellular processes as a product of normal respiration and oxidative burst in immune cells [2].”
BackgroundTargeting the Antioxidant Enzymes for the Treatment of Reactive Oxygen Species (ROS)-Induced Cancer
Krishnamoorthy, S., Babu, K. N., Periyasamy, L., Stanley, J. A., Ramachandran, I., Kumaran, R., & Muthusami, S. (2022) · Handbook of Oxidative Stress in Cancer: Therapeutic Aspects · doi:10.1007/978-981-16-5422-0_219 · Cited by 3 · see citing works
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“Copper takes an active part in oxidation–reduction reactions [53].”
Self-disintegrating protein-leaking microparticles for topical protein delivery
Voltà‐Durán, E., Sánchez, J. M., Favaro, M. T. D. P., Martínez-Cuentra, G., Contreras, E., Somma, A. D., López‐Laguna, H., Unzueta, U., Casanova, I., Mangues, R., et al. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.147730 · Cited by 2 · see citing works
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“It is also an essential component of antioxidant enzymes, such as Cu-Zn superoxide dismutase (Cu, Zn SOD), the enzyme that protects skin and its appendages against ROS [165].”
Sánchez-Álvarez, A. O., Melendez, J. A., Silvestry-Ramos, M., & Cabrera, C. R. (2023) · Journal of the Mexican Chemical Society · doi:10.29356/jmcs.v67i4.1963 · Cited by 2 · see citing works
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Li, C., Majd, M. H., Heidari, A., Razmara, Z., & Guo, D. (2025) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/0118715206380073250811113008 · Cited by 1 · see citing works
Monitoring Minerals and Redox Balance During Cyclosporine A Therapy in Psoriasis
Grabarek, B. O., Kulej, W., Wójcik, M., Stefaniak, M., Plata-Babula, A., Ordon, P., Michalski, P., & Michalska‐Bańkowska, A. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14227908 · Cited by 1 · see citing works
“Zn’s steady increase is clinically meaningful given its central involvement in keratinocyte differentiation, metalloproteinase modulation, cytokine signaling, and superoxide dismutase functioning [44,45].”
Yousif, A. T., Saliem, S. S., & Ibrahim, S. M. (2025) · The Open Dentistry Journal · doi:10.2174/0118742106414754250902072707 · Cited by 1 · see citing works
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Oxidative stress, varicocele, and disorders of male reproduction
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“Mn-SOD is mostly located in the mitochondrial matrix, whereas Cu/Zn-SOD is found in the cytoplasm (Altobelli et al. 2020).”
Hubungan Kadar Cuprum dan Malondialdehyde Pada Kehamilan
Ariani, N. (2021) · Jurnal Indonesia Sosial Sains · doi:10.36418/jiss.v2i3.212 · Cited by 1 · see citing works
Antioxidant Agents for Treatment and Prevention of Patients with Atopic DermatitisPreprint
SIMONI, E. D., Candelora, M., Belleggia, S., Molinelli, E., Rizzetto, G., Ferretti, G., Bacchetti, T., Capodaglio, I., Offidani, A., & Simonetti, O. (2023) · Preprints.org · doi:10.20944/preprints202306.2234.v1
Targeting the Antioxidant Enzymes for the Treatment of Reactive Oxygen Species (ROS)-Induced Cancer
Krishnamoorthy, S., Babu, K. N., Periyasamy, L., Stanley, J. A., Ramachandran, I., Ramachandran, I. K., & Muthusami, S. (2022) · Handbook of Oxidative Stress in Cancer: Therapeutic Aspects · doi:10.1007/978-981-16-1247-3_219-1
Targeting the Antioxidant Enzymes for the Treatment of Reactive Oxygen Species (ROS)-Induced Cancer
Krishnamoorthy, S., Babu, K. N., Periyasamy, L., Stanley, J. A., Ramachandran, I., Ramachandran, I. K., & Muthusami, S. (2022) · Handbook of Oxidative Stress in Cancer: Therapeutic Aspects · doi:10.1007/978-981-16-1247-3_219-2
Evaluation of serum mineral status in dermatological disorders of dogs
Sai, G. S., Babitha, V., Ramnath, V., Beena, V., & Unny, N. M. (2023) · Journal of Veterinary and Animal Sciences · doi:10.51966/jvas.2023.54.2.354-359
“This in turn might have overutilised or exhausted the available serum zinc and copper levels for the biosynthesis of various antioxidant enzymes like copper/ zinc superoxide dismutase (Cu-Zn SOD), to neutralize reactive oxygen species generated (Altobelli et al., 2020).”
BackgroundResultInfluentialАКТУАЛЬНІ АСПЕКТИ РЕПАРАТИВНОЇ РЕГЕНЕРАЦІЇ ШКІРИ: СУЧАСНИЙ ПОГЛЯД НА ПРОБЛЕМУ
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Ajiboye, B. O., Ayemoni, F. I., Famusiwa, C. D., Lawal, O. E., Falode, J. A., Onikanni, S. A., Akhtar, M. F., Gupta, S., & Oyinloye, B. E. (2025) · Journal of Molecular Histology · doi:10.1007/s10735-025-10366-x
“Zinc also plays a part in alleviating oxidative stress via its normoglycemic ability and glucose transport-enhancing ability (Altobelli et al. 2020; Choi et al. 2020).”
Keet, L., Deepnarain, N., Willemse, D., Abel, S., Louw, A., & Lilly, M. (2025) · Journal of Photochemistry and Photobiology · doi:10.1016/j.jpap.2025.100263
Zhang, Y., Nan, Z., Korma, S. A., Chen, S., & Li, L. (2025) · International Journal of Food Science & Technology · doi:10.1093/ijfood/vvaf121
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“When zinc availability is reduced, Cu/Zn-SOD’s activity is impaired, making cells more susceptible to elevated reactive oxygen species (ROS) and enhancing the oxidative damage caused by NO [35, 36].”
Xu, B., Hou, H., Xiao, T., Chen, C., & Liu, Q. (2025) · Aquaculture Nutrition · doi:10.1155/anu/5521491
“SOD is a crucial indicator of antioxidant capacity and nonspeci fi c immune function, playing a critical role in scavenging oxygen free radicals and reducing reactive oxygen species [31].”
Marine enzymes—Production, scale-up, and applications
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“Under Cu deficiency, reduced activity of cop - per–superoxide dismutase (Cu–SOD) and ceruloplasmin in the antioxidant defence system leads to excessive production of reactive oxygen species (ROS) [36, 37].”
Biomimetic Protein Materials for Adjuvant-Free Dermal Penetration
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Effect of adsorption condition on Vitamin C capture in FAU zeolite
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“Vitamin C (VitC) is a water-soluble antioxidant essential for collagen synthesis [1], immune function, and iron absorption, with recognized roles in preventing scurvy, enhancing wound healing, and protecting against oxidative stress [2].”
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Serum and Plasma Zinc and Copper Levels in Oral Leukoplakia: A Systematic Review and Meta-Analysis
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“Zinc (Zn) also appears to influence cutaneous antioxidant defense and immune function in a dose-and context-dependent manner (Altobelli et al. 2020).”
Copper overload induces oxidative stress in mesenteric PVAT and modulates vascular reactivity
Mawandji, N. B. D. S., Schereider, I. R. G., Vieira, J. M., Lisboa, N. A. D. S., Nunes, K. Z., Vassallo, D. V., & Lopes, A. B. (2026) · BioMetals · doi:10.1007/s10534-026-00904-9
- Authors
- Altobelli, G. G., Van Noorden, S., Balato, A., & Cimini, V.
- Affiliations
- University of Naples Federico II (IT)
- Corresponding author
- Altobelli, Giovanna G.
- Cimini, Vincenzo
- Venue
- Frontiers in Medicine
- Publisher
- Frontiers Media SA
- Published
- 2020-05-12
- Volume
- 7
- Pages
- 183-183
- ISSN
- 2296-858X (ISSN-L)
- PMC
- PMC7235401
- OpenAlex
- W3025365823
- Cited by
- 84
- References
- 96
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 13 · 2023: 13 · 2022: 18 · 2021: 9
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- copper-zinc superoxide dismutase, human skin, keratinocytes, reactive oxygen species, oxidative stress, skin appendages, enzyme subcellular localization, gender and age differences, antioxidant enzymes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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