Relationship of cholesterolgenesis to DNA synthesis and proliferation by lens epithelial cells in culture.
Cholesterolgenesis could be important for both cell growth and DNA synthesis in many cell types. Since the ocular lens seems at least partially dependent upon biosynthesis to supply its required cholesterol, cholesterolgenesis could have a special role in control of cell proliferation and DNA synthesis in the lens. We thus examined the effects of inhibiting sterol synthesis with mevinolin upon cell proliferation, upon accumulation of DNA, sterol and protein mass and upon DNA synthesis by bovine lens epithelial cells cultured in lipoprotein-deficient media. All DNA synthesis in the ocular lens occurs in the monolayer of epithelial cells which covers the anterior surface of this organ. Concentrations of mevinolin which largely prevented synthesis and accumulation of sterol by the cultured lens epithelial cells and stopped proliferation of these cells had no effect on the cell's DNA synthesis or accumulation of DNA mass. The inhibition of proliferation by mevinolin could be completely reversed by cholesterol added to the culture media in the form of low density lipoprotein. These findings indicate that an adequate supply of cholesterol is required by lens epithelial cells to proceed through the cell cycle. Inhibition of cholesterolgenesis by the lens in vivo could have profound effects upon lens growth and development.
el-Sayed
G N
GN
Department of Biochemistry, Kirksville College of Osteopathic Medicine, MO 63501.
Cenedella
R J
RJ
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002417:Cattle; D002452:Cell Count; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D013261:Sterols / Q000096:biosynthesis
D000924:Anticholesteremic Agents; D008077:Lipoproteins, LDL; D013261:Sterols; D004247:DNA; D002784:Cholesterol; D008148:Lovastatin