Chonnam Med J.  2005 Apr;41(1):89-96.

Effect of Protein Kinase C on UVB-induced p53, Fas and Fas Ligand

• Kim YJ
• Yun SJ
• Lee JB
• Kim SJ
• Won YH

Abstract

It is well known that ultraviolet (UV)-induced cell death is mediated by two main pathways of p53 and Fas/Fas ligand (FasL) pathway in the skin. Protein kinase C (PKC) plays a central role in the transduction of external signals at the intracellular level and is known to regulate a variety of cell functions, such as proliferation and differentiation. However, the exact molecular mechanism of cell death and the role of PKC in it still remain unclear. This study was aimed to evaluate the effect of PKC on UVB-induced p53 and Fas/FasL expression. The HaCaT cells of keratinocytes and normal human skin fibrioblasts (HSF) were irradiated with UVB in doses of 20 mJ/cm2. Some of the cells were stimulated by phorbol 12-myristate 13-acetate (PMA) 100 nM as a PKC activator for 24 h. Cell viabilities was assayed by MTT assay, and the expression of p53, Fas and FasL were analysed by Western blot anaylsis. p53 expression of HaCaT cells up-regulated at once by the UVB irradiation and progressed until 3 h and then down-regulated gradually, and the up-regulation was inhibited by PMA stimulation in its range of 67~95% (relative density). As far the HSF, the increase of p53 started at 3 h and advanced until 24 h, and the increase was inhibited by PMA stimulation in its range of 32~42%. Fas expression of HaCaT cells was constitutionally expressed; but it was not significantly changed by the UVB irradiation. However, the PMA pretreatment resulted in the increase of Fas protein by UVB irradiation. In the HSF, however, Fas was progressively up-regulated from the start to 24 h. PMA pretreatment inhibited the increase at 24 h. FasL expression was increased in a time-dependent pattern in the both cell types. However, they were not altered by the PMA stimulation. The results suggest that UVB cause cell death through the induced p53, Fas and FasL, which may be differently modulated according to cell types by PKC.

Keyword

Fas; FasL; p53; PKC; UVB

MeSH Terms

Blotting, Western
Cell Death
Cell Survival
Constitution and Bylaws
Fas Ligand Protein*
Humans
Keratinocytes
Protein Kinase C*
Protein Kinases*
Skin
Up-Regulation
Fas Ligand Protein
Protein Kinase C
Protein Kinases