Nicholas A Delamere

Nicholas A Delamere

Department Head, Physiology
Professor, Physiology
Professor, Ophthalmology
Member of the Graduate Faculty
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-6425

Research Interest

Nicholas Delamere, Ph.D., studies how ocular pressure (pressure in the eye) is controlled and the way cells transport fluid, and seeks to find methods to regulate the mechanisms involved. His goal is to develop drugs that reduce intraocular pressure, thereby decreasing the severity of glaucoma and damage to the retina. His cataract research also offers a promising model for tissue preservation, which will delay the onset of cataracts. https://delamerelab.medicine.arizona.edu/

Publications

Delamere, N. A., Shahidullah, M., J, B. M., M, A. J., C, L. J., & J, X. (2014). Mechanosensitive release of adenosine 5'-triphosphate pannexin channels and mechanosensitive upregulation of pannexin channels in potic nerve head astrocytes: A mechanism for purinergic involvement in chronic strain.. Glia.
Bozulic, L. D., Dean, W. L., & Delamere, N. A. (2004). The influence of Lyn kinase on Na,K-ATPase in porcine lens epithelium. American journal of physiology. Cell physiology, 286(1), C90-6.

Na,K-ATPase is essential for the regulation of cytoplasmic Na+ and K+ levels in lens cells. Studies on the intact lens suggest activation of tyrosine kinases may inhibit Na,K-ATPase function. Here, we tested the influence of Lyn kinase, a Src-family member, on tyrosine phosphorylation and Na,K-ATPase activity in membrane material isolated from porcine lens epithelium. Western blot studies indicated the expression of Lyn in lens cells. When membrane material was incubated in ATP-containing solution containing partially purified Lyn kinase, Na,K-ATPase activity was reduced by approximately 38%. Lyn caused tyrosine phosphorylation of multiple protein bands. Immunoprecipitation and Western blot analysis showed Lyn treatment causes an increase in density of a 100-kDa phosphotyrosine band immunopositive for Na,K-ATPase alpha1 polypeptide. Incubation with protein tyrosine phosphatase 1B (PTP-1B) reversed the Lyn-dependent tyrosine phosphorylation increase and the change of Na,K-ATPase activity. The results suggest that Lyn kinase treatment of a lens epithelium membrane preparation is able to bring about partial inhibition of Na,K-ATPase activity associated with tyrosine phosphorylation of multiple membrane proteins, including the Na,K-ATPase alpha1 catalytic subunit.

Salyer, S. A., Olberding, J. R., Distler, A. A., Lederer, E. D., Clark, B. J., Delamere, N. A., & Khundmiri, S. J. (2013). Vacuolar ATPase driven potassium transport in highly metastatic breast cancer cells. Biochimica et biophysica acta, 1832(10), 1734-43.

Breast cancer is the second leading cause of death in women and thus has received a great deal of attention by researchers. Recent studies suggested decreased occurrence of cancer in patients treated with cardiac glycosides (CGs) for heart conditions. Because CGs induce their cellular effects via the Na(+), K(+) ATPase (Na-K), we treated four breast cancer cell lines (MCF-7, T47D, MDA-MB453, and MDA-MB231) and a non-cancerous breast ductal epithelial cell line (MCF-10A) with ouabain, a well-characterized CG, and measured cell proliferation by measuring bromodeoxyuridine incorporation. Ouabain (1μM) decreased cell proliferation in all cell lines studied except MDA-MB453 cells. Western blot of Na-K α and β subunits showed α1, α3, and β1 expression in all cell lines except MDA-MB453 cells where Na-K protein and mRNA were absent. Potassium uptake, measured as rubidium ((86)Rb) flux, and intracellular potassium were both significantly higher in MDA-MB453 cells compared to MCF-10A cells. RT-qPCR suggested a 7 fold increase in voltage-gated potassium channel (KCNQ2) expression in MDA-MB453 cells compared to MCF-10A cells. Inhibition of KCNQ2 prevented cell growth and (86)Rb uptake in MDA-MB453 cells but not in MCF-10A cells. All cancer cells had significantly higher vacuolar H-ATPase (V-ATPase) activity than MCF-10A cells. Inhibition of V-ATPase decreased (86)Rb uptake and intracellular potassium in MDA-MB453 cells but not in MCF-10A cells. The findings point to the absence of Na-K, high hERG and KCNQ2 expression, elevated V-ATPase activity and sensitivity to V-ATPase inhibitors in MDA-MB453. We conclude that cancer cells exhibit fundamentally different metabolic pathways for maintenance of intracellular ion homeostasis.

Shahidullah, M., Mandal, A., Beimgraben, C., & Delamere, N. A. (2012). Hyposmotic stress causes ATP release and stimulates Na,K-ATPase activity in porcine lens. Journal of cellular physiology, 227(4), 1428-37.

Purinergic receptors in lens epithelium suggest lens function can be altered by chemical signals from aqueous humor or the lens itself. Here we show release of ATP by intact porcine lenses exposed to hyposmotic solution (200 mOsm). 18α-glycyrrhetinic acid (AGA) added together with probenecid eliminated the ATP increase. N-ethylmaleimide (200 µM), an exocytotic inhibitor, had no significant effect on ATP increase. Lenses exposed to hyposmotic solution displayed a ~400% increase of propidium iodide (PI) entry into the epithelium. The increased ability of PI (MW 668) to enter the epithelium suggests possible opening of connexin and/or pannexin hemichannels. This is consistent with detection of connexin 43, connexin 50, and pannexin 1 in the epithelium and the ability of AGA + probenecid to prevent ATP release. Na,K-ATPase activity doubled in the epithelium of lenses exposed to hyposmotic solution. The increase of Na,K-ATPase activity did not occur when apyrase was used to prevent extracellular ATP accumulation or when AGA + probenecid prevented ATP release. The increase of Na,K-ATPase activity was inhibited by the purinergic P2 antagonist reactive blue-2 and pertussis toxin, a G-protein inhibitor, but not by the P2X antagonist PPADS. Hyposmotic solution activated Src family kinase (SFK) in the epithelium, judged by Western blot. The SFK inhibitor PP2 abolished both SFK activation and the Na,K-ATPase activity increase. In summary, hyposmotic shock-induced ATP release is sufficient to activate a purinergic receptor- and SFK-dependent mechanism that stimulates Na,K-ATPase activity. The responses might signify an autoregulatory loop initiated by mechanical stress or osmotic swelling.

Henriksen, E. J., Atwater, A. E., Delamere, N. A., & Dantzler, W. H. (2011). The Physiology undergraduate major in the University of Arizona College of Medicine: past, present, and future. Advances in physiology education, 35(2), 103-9.

The American Physiological Society (APS) and APS Council encourage the teaching of physiology at the undergraduate, graduate, and medical school levels to support the continued prominence of this area of science. One area identified by the APS Council that is of particular importance for the development of future physiologists (the "physiology pipeline") is the teaching of physiology and physiology-related topics at the undergraduate level. In this article, we describe the historical development and implementation of an undergraduate program offered through the Department of Physiology, a basic science department in the College of Medicine at the University of Arizona, culminating in a Bachelor of Science in Health Sciences degree with a major in Physiology. Moreover, we discuss the current Physiology curriculum offered at our institution and explain how this program prepares our students for successful entry into a variety of postbaccalaureate professional programs, including medical school and numerous other programs in health professions, and in graduate study in the Masters and Doctoral programs in biomedical sciences. Finally, we cover the considerable challenges that we have faced, and continue to face, in developing and sustaining a successful physiology undergraduate major in a college of medicine. We hope that the information provided on the Physiology major offered by the Department of Physiology in the College of Medicine at the University of Arizona will be helpful for individuals at other institutions who may be contemplating the development and implementation of an undergraduate program in Physiology.