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Role of small GTP-binding proteins in lovastatin induced cataracts

Publication ,  Conference
Rao, PV
Published in: Investigative Ophthalmology and Visual Science
December 1, 1997

Purpose. To investigate suppression of isoprenylation of small GTP-binding proteins as a possible causative biochemical mechanism involved in lovastatin induced cataractogenesis. Methods. The effects of lovastatin on lens epithelial cell proliferation and morphology and on lens transparency have been carried out using cultured epithelial cells from human and rabbit lenses, and organ-cultured rat lenses, respectively. Results. Rat lenses organ cultured with lovastatin, a 3hydroxy-3-methyl glutaryl (HMG)-CoA reductase inhibitor, for one week developed frank subcapsular opacity. Lens epithelial cells (both human and rabbit} demonstrated extensive morphological changes and inhibition of proliferation when treated with lovastatin. Incubation of lenses or lens epithelial cells with both lovastatin and DL-mevalonic acid (a precursor of isoprenoids whose synthesis is inhibited by lovastatin) prevented lovastatin induced changes, whereas incubation with cholesterol and lovastatin did not prevent the changes. An accumulation of GTP-binding proteins in the soluble fractions of lovastatin treated lens epithelial cells was consistent with a blockade in their isoprenylation thereby preventing normal association with membranes. Conclusions. Small GTP-binding proteins play fundamental roles in various cellular processes including growth, differentiation and maintenance of cell morphology. The findings suggest that impairment of the function of small GTP-binding proteins due to blockade in isoprenylation, affects lens cell morphology and proliferation, and induces lens opacity in vitro. None.

Duke Scholars

Published In

Investigative Ophthalmology and Visual Science

ISSN

0146-0404

Publication Date

December 1, 1997

Volume

38

Issue

4

Related Subject Headings

  • Ophthalmology & Optometry
  • 11 Medical and Health Sciences
  • 06 Biological Sciences
 

Citation

APA
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ICMJE
MLA
NLM
Rao, P. V. (1997). Role of small GTP-binding proteins in lovastatin induced cataracts. In Investigative Ophthalmology and Visual Science (Vol. 38).
Rao, P. V. “Role of small GTP-binding proteins in lovastatin induced cataracts.” In Investigative Ophthalmology and Visual Science, Vol. 38, 1997.
Rao PV. Role of small GTP-binding proteins in lovastatin induced cataracts. In: Investigative Ophthalmology and Visual Science. 1997.
Rao, P. V. “Role of small GTP-binding proteins in lovastatin induced cataracts.” Investigative Ophthalmology and Visual Science, vol. 38, no. 4, 1997.
Rao PV. Role of small GTP-binding proteins in lovastatin induced cataracts. Investigative Ophthalmology and Visual Science. 1997.

Published In

Investigative Ophthalmology and Visual Science

ISSN

0146-0404

Publication Date

December 1, 1997

Volume

38

Issue

4

Related Subject Headings

  • Ophthalmology & Optometry
  • 11 Medical and Health Sciences
  • 06 Biological Sciences