title: Pre-elafin is Involved in Ultraviolet-induced Keratinocyte Apoptosis via Pro-caspase-3 Activation Associated with Cystatin-A Down-regulation.
abstract: Pre-elafin controls keratinocyte integrity via cornified envelope formation and inhibition of desquamation, but its role in ultraviolet (UV)-induced keratinocyte apoptosis is unknown. This study examined the role of pre-elafin in volunteer skin samples and primary cultured normal human keratinocytes irradiated with phototoxic doses of UVA/narrow-band UVB, and in keratinocytes with pre-elafin overexpression/knockdown, under conditions of low and high calcium. Phototoxic doses of UV increased pre-elafin mRNA and protein expression in inverse proportion to keratinocyte survival. Pre-elafin overexpression under conditions of low calcium, which, in contrast to conditions of high calcium, was localized to the cytoplasm, increased keratinocyte apoptosis, whereas knockdown inhibited UV-induced apoptosis. Pre-elafin was co-localized with, but not bound to, cleaved caspase-3. Pre-elafin reduced cystatin-A expression, which was bound to pro-caspase-3. In conclusion, UV phototoxicity-induced pre-elafin inside keratinocytes prior to cornified envelope formation could be involved in UV-induced keratinocyte apoptosis via cystatin-A downregulation resulting in pro-caspase-3 activation.
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, 410-773 Goyang-si, Korea.
authors.forename: Hyangmi
authors.initials: H
authors.lastname: Kim
authors.forename: Minsoo
authors.initials: M
authors.lastname: Noh
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Ai-Young
authors.initials: AY
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism*; D002478:Cells, Cultured; D055312:Cystatin A / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D053492:Elafin / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D011485:Protein Binding; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000528:radiation effects; D012867:Skin / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects*; D014162:Transfection; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D055312:Cystatin A; D053492:Elafin; C506806:PI3 protein, human; D011498:Protein Precursors; C026407:CSTA protein, human; C505407:CASP3 protein, human; D053148:Caspase 3