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<<snip>>
UVA-induced necrotic cell death appears to reflect the intracellular level of
LIP (iron)
<<snip>>
J Invest Dermatol. 2004 Oct;123(4):771-80. Related Articles, Links
Susceptibility of Skin Cells to UVA-induced Necrotic Cell Death Reflects the
Intracellular Level of Labile Iron.
Zhong JL, Yiakouvaki A, Holley P, Tyrrell RM, Pourzand C.
Department of Pharmacy and Pharmacology, university of Bath, Bath, UK.
The mechanism of resistance of keratinocytes to ultraviolet A (UVA) (320-400
nm)-induced oxidative damage has not yet been elucidated. Here, we examined the
possible link between the intracellular level of the labile iron pool (LIP) and
the susceptibility to UVA-induced cell death using a series of human skin
fibroblast and keratinocyte cell lines as a model. Resistance of keratinocytes
to UVA-induced cell death was confirmed by flow cytometry and in fibroblasts
necrosis was found to be the primary mode of cell death induced by UVA. The
percentage of necrosis in fibroblasts also correlated with the extent of
intracellular ATP depletion, a hallmark of necrotic cell death. The evaluation
of the intracellular level of LIP by calcein assay revealed that both "basal"
and "UVA-induced" levels of LIP in keratinocytes were several fold lower than
in fibroblasts. Accordingly the dose to give an equivalent level of necrosis
was several fold lower in fibroblasts than in keratinocytes. Furthermore, the
modulation of "basal" or "UVA-induced" level of LIP by either Desferal and/or
hemin treatment significantly affected the extent of UVA-induced necrotic cell
death and ATP depletion in all the cell lines. Cellular susceptibility to
UVA-induced necrotic cell death appears to reflect the intracellular level of
LIP.
PMID: 15373784 [PubMed - in process]
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