Nerve growth factor rescues pigment cells from ultraviolet-induced apoptosis by upregulating BCL-2 levels.
Apoptosis plays an important role in eliminating dysfunctional damaged cells. For skin, the best characterized injurious environmental agent is ultraviolet (UV) irradiation. Most of the damaging UV irradiation is absorbed in the epidermis and leads to apoptosis of keratinocytes. However, epidermal melanocytes appear to be protected from UV-induced apoptosis. We now report that in pure cultures melanocytic cells undergo characteristic apoptosis after physiologic UV exposures. However, nerve growth factor (NGF) supplementation protects them from this programmed cell death. Furthermore, we show that NGF protects melanocytic cells from UV-induced apoptosis by upregulating BCL-2 protein in these cells and that prior downregulation of BCL-2 abrogates the NGF protective effect on melanocytes. Our data suggest that NGF, known to be constitutively produced by epidermal keratinocytes and induced in these cells after UV irradiation, may preserve the population of cutaneous melanocytes that would otherwise be depleted by casual sun exposure.
Zhai
S
S
Department of Dermatology, Boston University of Medicine, MA 02118-2394, USA.
Yaar
M
M
Doyle
S M
SM
Gilchrest
B A
BA
D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D001483:Base Sequence; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008544:Melanocytes / Q000187:drug effects* / Q000528:radiation effects; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000502:physiology
D009414:Nerve Growth Factors; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011505:Protein-Tyrosine Kinases