8-甲氧补骨脂素和长波紫外线在细胞光老化中对端粒缩短机制的影响

Objective To investigate the mechanism of telomere shortening through 8-methoxypsoralen(8-MOP)and subsequent ultraviolet A(UVA)irradiation-induced photoaging model in human dermal fibroblasts(HDFs).Methotis Photoaging model was established by 8-MOP+UVA in skin HDFs.Flow cytometer.enzyme eytochemistry,immunofluorescence,Westem blot and Real-time PCR were employed.Results The percentage of G1 blockage of 8-MOP+UVA group were higher than that of control group at 24、48、72 h and 7 d(61.4%±1.5% vs 32.8%±1.5%.69.5%±2.2% vs 44.9% ±2.3%.88.2%±1.6% vs 59.8%±1.4%,90.7%±2.5% vs 68.5%±2.6%.all P＜0.01).The expression of SA-β-Gal of 8-MOP+UVA group were higher than that of control group at 24、48、72 h and 7 d(34.87%±0.59% vs 7.11%±0.78%,59.38%±0.46% vs 10.57%±0.47%.72.46%±0.98% vs 11.67%±0.87%,94.33%±0.13% vs 12.04%±0.12%,all P＜0.01).8-MOP+UVA treatment could significantly aggravate the oxidative DNA damages,the percentage of 8-oxo-dG positive cell of 8-MOP+UVA group(95.78%±0.14%)were significantly higher than that of control group(7.69%±0.09%,P＜0.01),8-MOP group(9.76%±0.11%,P＜0.01)and UVA group(35.29%±0.14%,P＜0.05).8-MOP+UVA treatment could accelerate the telomere shortening.the relative length of telomere of 8-MOP +UVA group were 2.57±0.05 lower than that of control group(6.63±0.12.P＜0.01).The levels of P53,P21WAF-1 and P16INK-4a of 8-MOP+UVA group were higher than that of control group(3.00±0.88 vs 0.54±0.10,2.50±0.51 vs 0.42±0.06,2.21±0.34 vs 0.38±0.05,all P＜0.01).Conclusion 8-MOP+UVA-induced photoaging of HDFs can be mediated though the regulation of telomere and subsequent P53-dependent signaling pathways.

Mechanism of telomere shortening in photoaging model induced by 8-methoxypsoralen and ultraviolet A