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Response of Monovalent Cation Transporters to Pro-apoptotic Protein Kinase C Modulators in Human Lens Epithelial Cells

Lepera, Michael Anthony
http://rave.ohiolink.edu/etdc/view?acc_num=wright1314376525

Abstract Details

2011, Master of Science (MS), Wright State University, Pharmacology and Toxicology.
Protein kinase inhibition by staurosporine causes apoptotic volume decrease involving potassium (K) channels in immortalized human B3 lens epithelial cells (LECs). Here, the effect of two pro-apoptotic protein kinase C (PKC) inhibitors [12-O-tetradecanoyl-phorbol-13-acetate (TPA) and chelerythrine (CET)] were studied on membrane K transport in a fetal human LEC line (FHL124) by western blotting, immunofluorescence, ion flux, ATP, apoptosis, and biotinylation assays. Long term TPA exposure (0-6 h) inhibited 75% of Na-K-2Cl cotransport (NKCC). In contrast, short term (0-20 min) exposure to 50 µM CET reduced Na/K pump and NKCC by >90% and >70%, respectively, without retrieval from the membrane into the cytosol, loss of ATP and early signs of apoptosis. CET (10-30 µM) decreased cell K by 33%. Results suggest PKC modulation through the use of pro-apoptotic agents caused major early membrane changes independently affecting K channels, the Na/K pump and NKCC function, prior to rise of any significant apoptosis.
Peter Lauf, MD (Advisor)
Norma Adragna, PhD (Committee Member)
Thomas Brown, PhD (Committee Member)
David Cool, PhD (Committee Member)
128 p.
Pharmacology; Toxicology
pharmacology; toxicology

Recommended Citations

Citations

  • Lepera, M. A. (2011). Response of Monovalent Cation Transporters to Pro-apoptotic Protein Kinase C Modulators in Human Lens Epithelial Cells [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1314376525

    APA Style (7th edition)

  • Lepera, Michael. Response of Monovalent Cation Transporters to Pro-apoptotic Protein Kinase C Modulators in Human Lens Epithelial Cells. 2011. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1314376525.

    MLA Style (8th edition)

  • Lepera, Michael. "Response of Monovalent Cation Transporters to Pro-apoptotic Protein Kinase C Modulators in Human Lens Epithelial Cells." Master's thesis, Wright State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=wright1314376525

    Chicago Manual of Style (17th edition)

wright1314376525
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© 2011, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.