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UV radiation induces galectin-3 expression through both AP-1 and NF-kappaB signaling pathways

Galectin-3 is a 32 kDa lectin that specifically binds to â-galactose on the non-reducing termini of oligosaccharide structures. It was shown to be involved in many different biological processes, including growth regulation, cell differentiation, adhesion, neoplastic transformation and tumor metastasis. Using M3/38 monoclonal antibody we analyzed effects of UV radiation on the expression of galectin-3 in A1235 glioblastoma cells. We found that exposure to UV-C light (ë=254 nm, 40 and 80 J/m2) nearly doubles the expression of galectin-3 within the 1 h after the exposure, and that galectin-3 stays on the approximately same level for the next 24 h. Based on the published structure of the promotor region of human galectin-3 gene (LGALS3) and roles of AP-1 and NF-kB in the stress response, we speculated that these two transcription factors might also have a role in the regulation of galectin-3 expression after exposure to UV-C irradiation. To test this hypothesis we have used antisense-jun oligonucleotides and zL3-vs, a specific proteasome inhibitor that prevents degradation of IkB, and blocks transcriptional activation through NF-kB. Treatment of cells with antisense-jun oligonucleotides caused slow, but statistically significant, and continuos decrease in galectin-3. After 10 h of cultivation in the presence of antisense-jun, the level of galectin-3 was about 60% of the initial value. In the same time, in cells that were treated with nonsense-jun oligonucleotides, levels of galectin-3 did not change, suggesting that Jun is involved in the regulation of the basal level of galectin-3 expression. However, even when the expression of Jun was significantly attenuated by antisense-jun oligonucleotides, UV-C irradiation still caused some increase in galectin-3 and moreover this increase started within minutes after the exposure, when it is to early to see effects of newly-synthesized Jun. To see whether NF-kB is involved in the induction of galectin-3 by UV-C light, we have used zL3-vs to block transcriptional activation through NF-kB. Treatment of cells with zL3-vs did not have any effect on the basal level of galectin-3 in the first 4 h of incubation. However, when cells pre-treated with zL3-vs were exposed to UV-C radiation, the increase of galectin-3 that was visible in the control cells, was nearly completely absent. This suggested that the early phase of induction of galectin-3 following the exposure to UV-C radiation is mediated by NF-kB.

Galectin-3; UV light; AP-1; NF-kappaB

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