目的:研究小剂量长波紫外线(UVA)辐射对人体皮肤的累积效应。方法:以10名志愿者的臀部作为受试部位,共分为3个区域:阴性对照区域,不进行照射;小剂量照射区域和阳性对照区域分别进行UVA照射,每周照射3次,连续13周,共39次。其中小剂量照...目的:研究小剂量长波紫外线(UVA)辐射对人体皮肤的累积效应。方法:以10名志愿者的臀部作为受试部位,共分为3个区域:阴性对照区域,不进行照射;小剂量照射区域和阳性对照区域分别进行UVA照射,每周照射3次,连续13周,共39次。其中小剂量照射区域的累积剂量为50 J/cm^2;阳性对照区域的累积剂量为1 000J/cm^2。照射前后测定皮肤角质层含水量、经皮水分丢失(transepidermal water loss,TEWL)、pH值、皮肤颜色的L~*a~*b~*值和M、E值。取照射区皮肤组织进行苏木精-伊红染色、弹性纤维染色和免疫组化染色,观察表皮、角质层厚度、胶原纤维、弹性纤维的变化、基质金属蛋白酶(MMP)-1和人类长寿基因SIRT1的蛋白表达产物在UVA照射后的变化。结果:小剂量照射区域角质层含水量有下降趋势,TEWL有增加趋势,L~*值下降、M、a~*、E值升高,pH值无明显变化。皮肤的角质层和表皮厚度增加,真皮中的胶原纤维细碎、淡染,弹性纤维片断化。MMP-1和SIRT1的表达增加。结论:小剂量UVA照射可以引起皮肤光老化。展开更多
Objective Lidamycin, an enediyne antibiotic, leads to apoptosis and mitotic cell death of human tumor cells at high and low concentrations. The reason why tumor cells have distinct responses to lidamycin remains elusi...Objective Lidamycin, an enediyne antibiotic, leads to apoptosis and mitotic cell death of human tumor cells at high and low concentrations. The reason why tumor cells have distinct responses to lidamycin remains elusive. This study was to elucidate if cellular prosurvival molecules are involved in these responses. Methods Cleavage of chromatin and DNA was observed by chromatin condensation and agarose gel electrophoresis. Accumulation of rhodamine 123 in lidamycin-treated cells was assayed by flow cytometry. Cell multinucleation was detected by staining with Hoechst 33342. Western blot and senescence-associated β-galactosidase （SA-β-gal） staining were used to analyze protein expression and senescence-like phenotype, respectively. Results SIRT1 deacetylase remained unchanged in 0.5 nmol/L lidamycin whereas cleavage occurred when apoptosis was induced by lidamycin. Increased FOXO3a, SOD-1 and SOD-2 expression and transient phosphorylation of ERK were detected after exposure of human hepatoma BEL-7402 cells to 0.5 nmol/L lidamycin. High expressions of SIRT1 and Akt were found in colon carcinoma HCT116 p53 knock-out cells exposed to lidamycin. Degradation of PARP and p53 by lidamycin as a substitute for SIRT1 and Akt was confirmed with caspase inhibitor Q-VD-OPh and proteasome inhibitor MG132. Resistance to lidamycin-induced DNA cleavage was observed in breast cancer doxorubicin-resistant MCF-7 cells. This was not induced by P-glycoprotein as no accumulation of rhodamine 123 was detected in the resistant cells following exposure to lidamycin. In contrast to sensitive MCF-7 cells, a lower multinucleation rate for the resistant cells was measured following exposure to equal concentrations of lidamycin. Conclusions Cellular prosurvival molecules, such as SIRTI, Akt, SOD-1, SOD-2 and other unknown factors can influence the action of lidamycin on human tumor cells.展开更多
文摘目的:研究小剂量长波紫外线(UVA)辐射对人体皮肤的累积效应。方法:以10名志愿者的臀部作为受试部位,共分为3个区域:阴性对照区域,不进行照射;小剂量照射区域和阳性对照区域分别进行UVA照射,每周照射3次,连续13周,共39次。其中小剂量照射区域的累积剂量为50 J/cm^2;阳性对照区域的累积剂量为1 000J/cm^2。照射前后测定皮肤角质层含水量、经皮水分丢失(transepidermal water loss,TEWL)、pH值、皮肤颜色的L~*a~*b~*值和M、E值。取照射区皮肤组织进行苏木精-伊红染色、弹性纤维染色和免疫组化染色,观察表皮、角质层厚度、胶原纤维、弹性纤维的变化、基质金属蛋白酶(MMP)-1和人类长寿基因SIRT1的蛋白表达产物在UVA照射后的变化。结果:小剂量照射区域角质层含水量有下降趋势,TEWL有增加趋势,L~*值下降、M、a~*、E值升高,pH值无明显变化。皮肤的角质层和表皮厚度增加,真皮中的胶原纤维细碎、淡染,弹性纤维片断化。MMP-1和SIRT1的表达增加。结论:小剂量UVA照射可以引起皮肤光老化。
基金supported by grants from the National Natural Science Foundation of China (No. 30672482)the National 973 Program (No. 2009CB521807)
文摘Objective Lidamycin, an enediyne antibiotic, leads to apoptosis and mitotic cell death of human tumor cells at high and low concentrations. The reason why tumor cells have distinct responses to lidamycin remains elusive. This study was to elucidate if cellular prosurvival molecules are involved in these responses. Methods Cleavage of chromatin and DNA was observed by chromatin condensation and agarose gel electrophoresis. Accumulation of rhodamine 123 in lidamycin-treated cells was assayed by flow cytometry. Cell multinucleation was detected by staining with Hoechst 33342. Western blot and senescence-associated β-galactosidase （SA-β-gal） staining were used to analyze protein expression and senescence-like phenotype, respectively. Results SIRT1 deacetylase remained unchanged in 0.5 nmol/L lidamycin whereas cleavage occurred when apoptosis was induced by lidamycin. Increased FOXO3a, SOD-1 and SOD-2 expression and transient phosphorylation of ERK were detected after exposure of human hepatoma BEL-7402 cells to 0.5 nmol/L lidamycin. High expressions of SIRT1 and Akt were found in colon carcinoma HCT116 p53 knock-out cells exposed to lidamycin. Degradation of PARP and p53 by lidamycin as a substitute for SIRT1 and Akt was confirmed with caspase inhibitor Q-VD-OPh and proteasome inhibitor MG132. Resistance to lidamycin-induced DNA cleavage was observed in breast cancer doxorubicin-resistant MCF-7 cells. This was not induced by P-glycoprotein as no accumulation of rhodamine 123 was detected in the resistant cells following exposure to lidamycin. In contrast to sensitive MCF-7 cells, a lower multinucleation rate for the resistant cells was measured following exposure to equal concentrations of lidamycin. Conclusions Cellular prosurvival molecules, such as SIRTI, Akt, SOD-1, SOD-2 and other unknown factors can influence the action of lidamycin on human tumor cells.
