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 Citations (Scopus)

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
Externally publishedYes

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Crystallins
Metallothionein
Lenses
Epithelial Cells
Metals
Shock
Hot Temperature
Genes
Iron
Small Heat-Shock Proteins
Poisons
Chromium
Manganese
Nickel
Aluminum
Cadmium
Magnesium
Zinc
Copper
Spectrum Analysis

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Activation of metallothioneins and α-crystallin/sHSPs in human lens epithelial cells by specific metals and the metal content of aging clear human lenses. / Hawse, John R; Cumming, Jonathan R.; Oppermann, Brian; Sheets, Nancy L.; Reddy, Venkat N.; Kantorow, Marc.

In: Investigative Ophthalmology and Visual Science, Vol. 44, No. 2, 01.02.2003, p. 672-679.

Research output: Contribution to journalArticle

Hawse, John R ; Cumming, Jonathan R. ; Oppermann, Brian ; Sheets, Nancy L. ; Reddy, Venkat N. ; Kantorow, Marc. / Activation of metallothioneins and α-crystallin/sHSPs in human lens epithelial cells by specific metals and the metal content of aging clear human lenses. In: Investigative Ophthalmology and Visual Science. 2003 ; Vol. 44, No. 2. pp. 672-679.
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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.",
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T1 - Activation of metallothioneins and α-crystallin/sHSPs in human lens epithelial cells by specific metals and the metal content of aging clear human lenses

AU - Hawse, John R

AU - Cumming, Jonathan R.

AU - Oppermann, Brian

AU - Sheets, Nancy L.

AU - Reddy, Venkat N.

AU - Kantorow, Marc

PY - 2003/2/1

Y1 - 2003/2/1

N2 - 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.

AB - 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.

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