Activation of metallothioneins and α-crystallin/sHSPs in human lens epithelial cells by specific metals and the metal content of aging clear human lenses

John R. Hawse, Jonathan R. Cumming, Brian Oppermann, Nancy L. Sheets, Venkat N. Reddy, Marc Kantorow

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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, βB-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, βB-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.

Original languageEnglish (US)
Pages (from-to)672-679
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume44
Issue number2
DOIs
StatePublished - Feb 1 2003

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Activation of metallothioneins and α-crystallin/sHSPs in human lens epithelial cells by specific metals and the metal content of aging clear human lenses'. Together they form a unique fingerprint.

  • Cite this