[Mechanism of telomere shortening in photoaging model induced by 8-methoxypsoralen and ultraviolet A].
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).


METHODS
Photoaging model was established by 8-MOP + UVA in skin HDFs. Flow cytometer, enzyme cytochemistry, immunofluorescence, Western 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-beta-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, P21(WAF-1) and P16(INK-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).


CONCLUSIONS
8-MOP + UVA-induced photoaging of HDFs can be mediated though the regulation of telomere and subsequent P53-dependent signaling pathways.
Gao
Ying-ying
YY
Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, China.
Luo
Dan
D
Zhou
Bing-rong
BR
Li
Wei
W
Min
Wei
W
Lin
Bing-jiang
BJ
D002460:Cell Line / Q000187:drug effects / Q000528:radiation effects; D016922:Cellular Senescence / Q000187:drug effects* / Q000528:radiation effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008730:Methoxsalen / Q000494:pharmacology*; D018384:Oxidative Stress; D016615:Telomere / Q000187:drug effects* / Q000528:radiation effects*; D014466:Ultraviolet Rays
D008730:Methoxsalen