8‐METHOXYPSORALEN PLUS UVA INDUCES THE 72 kDa HEAT SHOCK PROTEIN IN ORGAN‐CULTURED NORMAL HUMAN SKIN

Abstract

The proteins induced by heat and other stressors, called heat shock proteins (HSP) or stress proteins, are considered to play a general role in protection from cellular injury. Exposure to UVA (320-400 nm) following application of 8-methoxypsoralen (8-MOP), termed PUVA is commonly used in the field of dermatology. In order to understand the induction of HSP in PUVA-treated human skin, indirect immunofluorescence using a monoclonal antibody specific for the 72 kDa HSP (HSP 72) was carried out in organ-cultured normal human skin that was treated with PUVA. When the organ-cultured skin was treated at 37 degrees for 1 h with 8-MOP at a final concentration of 10 or 100 micrograms/mL and exposed to UVA (51.3 kJ/m2), nuclear immunofluorescence of HSP 72 was detected in the epidermal cells 12 h after UVA irradiation. In contrast, the induction of HSP 72 was not detected either by UVA irradiation or 8-MOP treatment. These results suggest that PUVA treatment is one of the stressors for human skin, and DNA damage caused by PUVA induces HSP 72.

Expression of Heat Shock Protein 70 in Human Skin Cells as a Photoprotective Function after UV Exposure

“…However, Trautinger et al 24 indicated that human keratinocytes constitutively express significant amounts of Hsp70. They 24 explained this discrepancy may be due to different techniques, in particular to a higher sensitivity of their three-step immunochemical techniques, as compared to the indirect immunofluorescence of Muramatsu et al 7,27 . These different results raise the question as to whether UV exposure induces expression of HSP70 in normal human keratinocytes.…”

“…The expression of Hsp70 may be further induced in epidermal keratinocytes by heat treatment, providing a state of resistance against the deleterious effects of heat 16 . UV-induced HSP70 expression was first reported by Muramatsu et al 7,27 in normal human skin system by an immunofluorescence method; Hsp70 expression was not detected at baseline 7,27 . However, Trautinger et al 24 indicated that human keratinocytes constitutively express significant amounts of Hsp70.…”

“…Keyse and Tyrrell 30 found 32 kD HSP after UVA exposure in EK4 fibroblasts and this HSP may be involved in a photoprotective function. Muramatsu et al 7,27 suggested that a possible mechanism of inducing HSP expression in UV irradiated fibroblasts was due to UV-labile proteins or UV-induced DNA damage. Trautinger et al 31 reported the expression of HSP72 after UVA radiation in a human fibrosarcoma cell line and suggested that induction of HSP72 is part of an adaptive response mechanism in human cells to UV-related stress.…”

“…This conservation implicates that HSP are necessary for successful survival under hostile environmental conditions 4 . In addition to heat, a wide variety of other stress factors, including chemicals (heavy metals and amino acid analogs), glucose starvation, pathogens, and states of diseases, have been described as inducers of HSP expression [5][6][7] . These proteins are therefore referred to as stress proteins 6,8 .…”

Expression of p53-regulated genes in human cultured lymphoblastoid TSCE5 and WTK1 cell lines after spaceflight in a frozen state

“…An accumulation of Hsp72 is induced not only by heat, but also by inducers of DNA damage in cultured human cells (Muramatsu et al, 1992(Muramatsu et al, , 1993(Muramatsu et al, , 1996Matsumoto et al, 1995). It was reported that HSP gene expression was depressed in rat muscle after experiencing spaceflight, and this was associated with a reduction in mechanical and neural activity levels (Ishihara et al, 2008).…”