Ultraviolet B-mediated phosphorylation of the small heat shock protein HSP27 in human keratinocytes

Exposure of human keratinocytes to environmental stress is known to induce changes in the expression, phosphorylation, and subcellular relocalization of the 27 kDa heat shock protein. This study demonstrates that ultraviolet B (280-320 nM) irradiation with physiologic doses induces a dose-dependent phosphorylation of 27 kDa heat shock protein, generating the more acidic 27 kDa heat shock protein B, C, and D isoforms, Ultraviolet B also induces pe rinuclear cytoplasmic relocation and nuclear translocation of 27 kDa heat s hock protein and caused aggregation of cytoplasmic actin filaments into a b road perinuclear distribution. The ultraviolet B-induced phosphorylation is reversible, returning to baseline levels 4 h after exposure, and this coin cides with the reversal of ultraviolet B-induced actin reorganization. The ultraviolet B-induced phosphorylation is not affected by the protein kinase C inhibitor, GF 109203X, is partially inhibited by epidermal growth factor receptor tyrosine kinase inhibitor, PD 153035, and is substantially inhibi ted by the specific p38 mitogen-activated protein kinase inhibitor, SE 2035 80, In addition, pretreatment of cells with the anti-oxidant N-acetyl cyste ine partially inhibits ultraviolet B-and oxidant-induced 27 kDa heat shock protein phosphorylation, The p38 mitogen-activated protein kinase cascade i s thus the major transduction pathway for ultraviolet B-induced 27 kDa heat shock protein phosphorylation, and reactive oxygen species generated in re sponse to ultraviolet B also contribute to this phosphorylation. As 27 kDa heat shock protein phosphorylation and relocalization has been associated w ith increased cell survival after environmental insult, our data suggest th at ultraviolet B, in addition to initiating recognized cytotoxic events in keratinocytes, also initiates a signaling pathway that may provide cellular protection against this ubiquitous environmental insult.