Premature avian melanocyte death due to low antioxidant levels of protection: fowl model for vitiligo.
Feather melanocytes in the Barred Plymouth Rock (BPR) and White Leghorn (WL) chickens die prematurely in vivo when compared to the wild type Jungle Fowl (JF) chicken. Since these mutant melanocytes live in vitro, an environmental factor in the feather must precipitate their death. Results show that the addition of selected antioxidants, glutathione (GSH) and superoxide dismutase (SOD), can rescue these mutant melanocytes in vitro that have been placed under stress conditions that cause their premature cell death. Measurements of in vivo levels of GSH, catalase, and SOD show no significant difference in catalase activity between the JF, BPR, and WL feathers but do show a significant reduction in GSH activity in both the BPR and WL feathers to approximately 66% of the GSH concentration found in JF feathers. SOD activity in the BPR tissue is reduced significantly to approximately 50% of the JF activity and the WL SOD activity is reduced significantly to approximately 50% of the BPR SOD activity. Preliminary results of measurements of glutathione peroxidase activity indicate there is no difference in the levels of this enzyme in JF, BPR and WL feathers. A working hypothesis, based on current results, is proposed for premature cell death in BPR and WL feather melanocytes. The BPR melanocytes are genetically sensitive due to a defect in their SOD and GSH levels caused by the barring gene (B) and their death, due to reactive species of oxygen radicals, is precipitated in the poorly vascularized feather by the accumulation of oxygen radicals due to the low turnover of tissue fluids. The WL chicken carries the dominant white gene (I) in addition to the B gene. This gene directs the further reduction of the level of SOD and, when combined with the cell death mechanism already present in the BPR chicken, causes the WL feather melanocytes to die much earlier than the BPR feather melanocytes which in turn die much earlier than the wild type JF melanocytes. This same mechanistic hypothesis could apply as a cause of premature melanocyte cell death in human vitiligo wherein the vitiliginous melanocytes may have a genetic defect in their oxygen radical protection system.
Bowers
R R
RR
Department of Biology, California State University, Los Angeles 90032.
Lujan
J
J
Biboso
A
A
Kridel
S
S
Varkey
C
C
D000818:Animals; D002374:Catalase / Q000032:analysis / Q000494:pharmacology; D016923:Cell Death; D002478:Cells, Cultured; D002645:Chickens / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005241:Feathers / Q000737:chemistry / Q000473:pathology*; D005978:Glutathione / Q000172:deficiency* / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000032:analysis; D017496:Hypopigmentation / Q000235:genetics*; D007980:Levodopa / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects / Q000473:pathology*; D008954:Models, Biological; D009154:Mutation; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000494:pharmacology; D014820:Vitiligo; D000521:alpha-MSH / Q000494:pharmacology
D017382:Reactive Oxygen Species; D007980:Levodopa; D000521:alpha-MSH; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione