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Increased susceptibility to oxidative stress‐ and ultraviolet A‐induced apoptosis in fibroblasts in atypical progeroid syndrome/atypical Werner syndrome with LMNA mutation
Author(s) -
Motegi Seiichiro,
Uchiyama Akihiko,
Yamada Kazuya,
Ogino Sachiko,
Yokoyama Yoko,
Perera Buddhini,
Takeuchi Yuko,
Ishikawa Osamu
Publication year - 2016
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13086
Subject(s) - lmna , progeria , lamin , oxidative stress , premature aging , cockayne syndrome , werner syndrome , apoptosis , biology , cancer research , microbiology and biotechnology , genetics , dna repair , endocrinology , gene , nucleotide excision repair , helicase , rna
Atypical progeroid syndrome ( APS ), including atypical Werner syndrome ( AWS ), is a disorder of premature ageing caused by mutation of the lamin A gene, the same causal gene involved in Hutchinson‐Gilford syndrome ( HGS ). We previously reported the first Japanese case of APS / AWS with a LMNA mutation (p.D300N). Recently, it has been reported that UVA induced abnormal truncated form of lamin A, called progerin, as well as HGS ‐like abnormal nuclear structures in normal human fibroblasts, being more frequent in the elderly, suggesting that lamin A may be involved in the regulation of photoageing. The objective of this study was to elucidate the sensitivity to cell damage induced by oxidative stress or UVA in fibroblasts from APS / AWS patient. Using immunofluorescence staining and flow cytometry analysis, the amount of early apoptotic cells and degree of intra‐cellular reactive oxygen species ( ROS ) generation were higher in H 2 0 2 ‐ or UVA ‐treated APS / AWS fibroblasts than in normal fibroblasts, suggesting that repeated UV exposure may induce premature ageing of the skin in APS / AWS patients and that protecting against sunlight is possibly important for delaying the emergence of APS / AWS symptoms. In addition, we demonstrated that H 2 O 2 ‐, or UVA ‐induced apoptosis and necrosis in normal and APS / AWS fibroblasts were enhanced by farnesyltransferase inhibitor ( FTI ) treatment, indicating that FTI might not be useful for treating our APS / AWS patient.