Activation of Metallothioneins and α-Crystallin/sHSPs in Human Lens Epithelial Cells by Specific Metals and the Metal Content of Aging Clear Human Lenses

• Published in: Investigative ophthalmology & visual science Vol. 44; no. 2; pp. 672 - 679
• Main Authors: Hawse, John R., Cumming, Jonathan R., Oppermann, Brian, Sheets, Nancy L., Reddy, Venkat N., Kantorow, Marc
• Format: Journal Article
• Language: English
• Published: Rockville, MD Association for Research in Vision and Ophtalmology 01.02.2003
• Subjects: Adult; Aged; Aging - physiology; alpha-Crystallins - biosynthesis; alpha-Crystallins - genetics; Biological and medical sciences; Cadmium - pharmacology; Cells, Cultured; Copper - pharmacology; Epithelial Cells - chemistry; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Heat-Shock Proteins - biosynthesis; Heat-Shock Proteins - genetics; Humans; Lens diseases; Lens, Crystalline - chemistry; Lens, Crystalline - drug effects; Lens, Crystalline - metabolism; Medical sciences; Metallothionein - biosynthesis; Metallothionein - genetics; Metals - analysis; Metals - pharmacology; Middle Aged; Ophthalmology; Reverse Transcriptase Polymerase Chain Reaction; Zinc - pharmacology; Human; Cataract; Pathophysiology; Ageing; Metal; Eye disease; Toxicology; Lens disease; Heat shock protein; Epithelial cell; Poison; Lens; Anterior segment disease; Metallothionein
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.02-0018

To identify those metallothionein and alpha-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. Human SRA01/04 and primary human lens epithelial cells were cultured and exposed to Cd(2+), Cu(2+), and Zn(2+). 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 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. 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 lens epithelial cells. Cd(2+) and Zn(2+), but not Cu(2+), induced the metallothioneins, whereas Cd(2+) and Cu(2+), but not Zn(2+), induced alphaB-crystallin and HSP27. alphaA-crystallin was induced by Cu(2+) only. Similar responses of the metallothionein IIa gene were detected in identically treated primary human lens epithelial cells. Cd(2+) and Zn(2+) 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. 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.