Toward mechanism-based antioxidant interventions: lessons from natural antioxidants.
It is generally accepted that one of the major and important contributions to skin aging, skin disorders, and skin diseases results from reactive oxygen species. More than other tissues, the skin is exposed to numerous environmental chemical and physical agents, such as ultraviolet light, causing oxidative stress. Accelerated cutaneous UV-induced aging, photo aging, is only one of the harmful effects of continual oxygen radical production in the skin. Interestingly, our ELISA assays of 8-oxo-2'-deoxyguanosine in skin of young and old Balb/c mice showed that cumene hydroperoxide-induced accumulation of the biomarker of oxidative DNA damage in skin of 32-week-old mice occurred independently of their vitamin E status, while no accumulation of oxo8-dG was detectable in the skin of young animals. This suggests that vitamin E is not the major protector of skin against cumene hydroperoxide-induced oxidative stress. Production and accumulation of apoptotic cells is one of the characteristic features of skin damage by oxidative stress that, in the absence of effective scavenging by macrophages, dramatically enhances oxidative damage and inflammatory response. In our model experiments, we demonstrated that Cu-OOH induces significant oxidative stress in phospholipids of normal human epidermal keratinocytes (NHEK) whose characteristic feature is an early and profound oxidation of phosphatidylserine (PS), likely related to PS externalization. Since externalized PS is a signal for recognition of apoptotic cells by macrophage scavenger receptors, PS oxidation may be translatable into elimination of thus damaged NHEKs. Experiments are now underway to determine whether inhibition of PS oxidation by antioxidants may interfere with important signaling functions of oxidative stress in eliminating apoptotic cells.
Kagan
Valerian E
VE
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. kagan@pitt.edu
Kisin
Elena R
ER
Kawai
Kazuaki
K
Serinkan
Behice F
BF
Osipov
Anatoly N
AN
Serbinova
Elena A
EA
Wolinsky
Ira
I
Shvedova
Anna A
AA
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000648:ultrastructure; D018384:Oxidative Stress; D010636:Phenols / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D010636:Phenols; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine