Activation of metallothioneins and α-crystallin/sHSPs in human lens epithelial cells by specific metals and the metal content of aging clear human lenses
Activation of metallothioneins and α-crystallin/sHSPs in human lens epithelial cells by specific metals and the metal content of aging clear human lenses
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DOI：
10.1167/iovs.02-0018
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发表时间：
2003-02-01
影响因子：
4.4
通讯作者：
Kantorow, M
中科院分区：
文献类型：
--
作者：
Hawse, JR;Cumming, JR;Kantorow, M
目的。鉴定人类数十个细胞中有毒金属诱导的金属硫蛋白和α-晶状体蛋白/小热休克基因，并评估年轻和老年人类晶状体之间这些金属的水平。培养人 SRA01/04 和原代人晶状体上皮细胞并暴露于 Cd2+、Cu2+ 和 Zn2+。采用半定量和定量竞争性RT-PCR分析晶状体金属硫蛋白（Ig、If、Ih、Ie和IIa）和α-晶状体蛋白/小热休克（αA-晶状体蛋白、αB-晶状体蛋白和HSP27）基因的水平。铝、镉、钙、铬、铜、铁、铅、镁、锰、镍、钾、钠和元素的含量采用电感耦合等离子体发射光谱法对年轻（平均 32.8 岁）、中年（平均 52.3 岁）和老年（平均 70.5 岁）人类晶状体中的锌进行分析。 结果。晶状体金属硫蛋白（Ig、If、Ih、Ie 和 IIa）和 α-晶状体蛋白/小热休克基因（αA-晶状体蛋白、αB-晶状体蛋白和 HSP27）在 SRA01/04 人日元上皮细胞中被特定金属差异诱导。 Cd2+ 和 Zn2+（而非 Cu2+）诱导金属硫蛋白，而 Cd2+ 和 Cu2+（而非 Zn2+）诱导 αB-晶状体蛋白和 HSP27。 αA-晶状体蛋白仅由 Cu2+ 诱导。在经过同样处理的原代人数十个上皮细胞中检测到金属硫蛋白 IIa 基因的类似反应。 Cd2+ 和 Zn2+ 诱导金属硫蛋白 IIa 的水平比金属硫蛋白 Ig 高五倍。在 13 种不同的金属中，只有铁发生了改变，与年轻镜片相比，老镜片的镜片减少了 81%。结论。不同金属对金属硫蛋白和α-晶状体蛋白/小热休克蛋白的诱导表明存在金属特异性晶状体调节途径，这些途径可能参与针对金属相关应力的保护。
PURPOSE. To identify those metallothionein and alpha-crystallin/ small heat-shock genes induced by toxic metals in human tens cells and to evaluate the levels of these metals between young and aged human lenses.Nests. Human SRA01/04 and primary human lens epithelial cells ere cultured and exposed to Cd2+, Cu2+, and Zn2+. The levels of lens metallothioneins (Ig, If, Ih, Ie, and IIa) and alpha-crystallin/small heat-shock (alphaA-crystallin, alphaB-crystallin, and HSP27) genes were analyzed by semiquantitative and quantitative competitive RT-PCR The content of aluminium, cadmium, calcium, chromium, copper, iron, lead, magnesium, manganese, nickel, potassium, sodium, and zinc in young (mean, 32.8 years), middle-aged (mean, 52.3 years), and old (mean, 70.5 years) human lenses was analyzed by inductively coupled plasma-emission spectroscopy.RESULTS. Lens metallothioneins (Ig, If, Ih, Ie, and IIa) and alpha-crystallin/small heat-shock genes (alphaA-crystallin, alphaB-crystallin, and HSP27) were differentially induced by specific metals in SRA01/04 human yens epithelial cells. Cd2+ and Zn2+, but not Cu2+, induced the metallothioneins, whereas Cd2+ and Cu2+, but not Zn2+, induced alphaB-crystallin and HSP27. alphaA-crystallin was induced by Cu2+ only. Similar responses of the metallothionein IIa gene were detected in identically treated primary human tens epithelial cells. Cd2+ and Zn2+ induced metallothionein IIa to five tithes higher levels than metallothionein Ig. Of 13 different metals, only iron was altered, exhibiting an 81% decrease in old versus young lenses.CONCLUSIONS. Induction of metallothioneins and alpha-crystallin/ small heat shock proteins by different metals indicates the presence of metal-specific lens regulatory pathways that are likely to be involved in protection against metal-associated stresses.