The effects of oxidative stress on telomerase activity and other stress-related proteins in lens epithelial cells.
Telomerase is a ribonucleoprotein complex responsible for maintaining the ends of chromosomes and for repair of DNA strand breaks. While telomerase activity is generally found in cells that have unlimited proliferative potential such as neoplastic cells, germline cells and some stem cells, lens epithelial cells (though not highly proliferative) have telomerase activity. Our previous studies indicated that lens epithelial cells express high levels of telomerase despite their low proliferative potential, thus we hypothesized that telomerase expression protects lens epithelial cells from oxidative stress. We also determined levels of the stress proteins gadd45 and p16 and the stress and proliferation-related protein, proliferating cell nuclear antigen (PCNA). In acute studies, lenses were exposed to TBHP for 0-120 min. In recovery studies, lenses were exposed to TBHP for 1 hr, then allowed to recover for up to 18 hr. In acute studies, telomerase activity was increased, p16 initially decreased then normalized, PCNA levels did not change significantly even in the overnight recovery groups, and gadd45 was decreased in some TBHP exposed groups. In recovery studies, telomerase activity was increased in all groups, gadd45 decreased then became elevated, and p16 levels were decreased at later recovery times. PCNA levels remained constant during the studies, indicating that there was no change in proliferation. These studies showed that elevated telomerase activity did not correlate with increased proliferation in lens epithelial cells; instead, increased telomerase activity was associated with increased levels of the stress-related protein gadd45 only in the later recovery times. These findings support the hypothesis that telomerase plays a protective rather than a proliferative role in lens epithelial cells.
Colitz
C M H
CM
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University College of Veterinary Medicine, 601 Vernon L Tharp Street, Columbus, OH 43210, USA. colitz.1@osu.edu
Whittington
A
A
Carter
R
R
Warren
J
J
D000818:Animals; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology; D000097642:GADD45 Proteins
D019941:Cyclin-Dependent Kinase Inhibitor p16; D005136:Eye Proteins; D019803:Glutathione Disulfide; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D019098:Telomerase; D020122:tert-Butylhydroperoxide; D000097642:GADD45 Proteins