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John R. Hawse, Jonathan R. Cumming, Brian Oppermann, Nancy L. Sheets, Venkat N. Reddy, Marc Kantorow; Activation of Metallothioneins and α-Crystallin/sHSPs in Human Lens Epithelial Cells by Specific Metals and the Metal Content of Aging Clear Human Lenses. Invest. Ophthalmol. Vis. Sci. 2003;44(2):672-679. doi: 10.1167/iovs.02-0018.
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purpose. To identify those metallothionein and α-crystallin/small heat-shock genes induced by toxic metals in human lens cells and to evaluate the levels of these metals between young and aged human lenses.
methods. Human SRA01/04 and primary human lens epithelial cells were cultured and exposed to Cd2+, Cu2+, and Zn2+. The levels of lens metallothioneins (Ig, If, Ih, Ie, and IIa) and α-crystallin/small heat-shock (αA-crystallin, αB-crystallin, and HSP27) genes were analyzed by semiquantitative and quantitative competitive RT-PCR. The content of aluminum, 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 α-crystallin/small heat-shock genes (αA-crystallin, αB-crystallin, and HSP27) were differentially induced by specific metals in SRA01/04 human lens epithelial cells. Cd2+ and Zn2+, but not Cu2+, induced the metallothioneins, whereas Cd2+ and Cu2+, but not Zn2+, induced αB-crystallin and HSP27. αA-crystallin was induced by Cu2+ only. Similar responses of the metallothionein IIa gene were detected in identically treated primary human lens epithelial cells. Cd2+ and Zn2+ induced metallothionein IIa to five times 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 α-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.
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