Low levels of glutathione are sufficient for survival of keratinocytes after UV irradiation and for healing of mouse skin wounds.
Reduced levels of the cellular antioxidant glutathione are associated with premature skin aging, cancer and impaired wound healing, but the in vivo functions of glutathione in the skin remain largely unknown. Therefore, we analyzed mice lacking the modifier subunit of the glutamate cysteine ligase (Gclm), the enzyme that catalyzes the rate-limiting step of glutathione biosynthesis. Glutathione levels in the skin of these mice were reduced by 70 %. However, neither skin development and homeostasis, nor UVA- or UVB-induced apoptosis in the epidermis were affected. Histomorphometric analysis of excisional wounds did not reveal wound healing abnormalities in young Gclm-deficient mice, while the area of hyperproliferative epithelium as well as keratinocyte proliferation were affected in aged mice. These findings suggest that low levels of glutathione are sufficient for wound repair in young mice, but become rate-limiting upon aging.
Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Otto-Stern-Weg 7, HPL F12, 8093, Zurich, Switzerland.
Michèle
M
Telorack
Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Otto-Stern-Weg 7, HPL F12, 8093, Zurich, Switzerland.|Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, 8057, Zurich, Switzerland.
Jeannette
J
Abplanalp
Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Otto-Stern-Weg 7, HPL F12, 8093, Zurich, Switzerland. Sabine.werner@biol.ethz.ch.
Sabine
S
Werner
D000375:Aging / Q000502:physiology* / Q000528:radiation effects; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D015603:Keratinocytes / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000235:genetics; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000473:pathology* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D014945:Wound Healing / Q000235:genetics
C560749:GCLM protein, mouse; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione
Glutathione; Skin; UV; Wound healing