Abstract
The Na+/H+-exchanger 1, NHE1 (SLC9A1) and the electroneutral Na+,HCO3 --cotransporter NBCn1 (SLC4A7) are coexpressed in a wide range of tissues. Under normal physiological conditions these transporters play an ostensibly similar role, namely that of net acid extrusion after cellular acidification. In addition, they have been implicated in multiple other cellular processes, including regulation of transepithelial transport, cell volume, cell death/survival balance, and cell motility. In spite of their apparent functional similarity, the two transporters also serve distinctly different functions and are differentially regulated. Here, we provide an update on the basic structure, function, regulation, physiology and pharmacology of NHE1 and NBCn1, with particular focus on the factors responsible for their functional similarities and differences. Finally, we highlight recent findings implicating these transporters in cancer development, and discuss issues relating to NHE1 and NBCn1 as potential targets in cancer treatment.
Keywords: SLC9A1, SLC4A7, cancer, acidification, bicarbonate, EIPA, cariporide, DIDS, S0859, Na+/H+-exchanger 1
Current Pharmaceutical Design
Title: Physiology, Pharmacology and Pathophysiology of the pH Regulatory Transport Proteins NHE1 and NBCn1: Similarities, Differences, and Implications for Cancer Therapy
Volume: 18 Issue: 10
Author(s): E. Boedtkjer, L. Bunch and S. F. Pedersen
Affiliation:
Keywords: SLC9A1, SLC4A7, cancer, acidification, bicarbonate, EIPA, cariporide, DIDS, S0859, Na+/H+-exchanger 1
Abstract: The Na+/H+-exchanger 1, NHE1 (SLC9A1) and the electroneutral Na+,HCO3 --cotransporter NBCn1 (SLC4A7) are coexpressed in a wide range of tissues. Under normal physiological conditions these transporters play an ostensibly similar role, namely that of net acid extrusion after cellular acidification. In addition, they have been implicated in multiple other cellular processes, including regulation of transepithelial transport, cell volume, cell death/survival balance, and cell motility. In spite of their apparent functional similarity, the two transporters also serve distinctly different functions and are differentially regulated. Here, we provide an update on the basic structure, function, regulation, physiology and pharmacology of NHE1 and NBCn1, with particular focus on the factors responsible for their functional similarities and differences. Finally, we highlight recent findings implicating these transporters in cancer development, and discuss issues relating to NHE1 and NBCn1 as potential targets in cancer treatment.
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Boedtkjer E., Bunch L. and F. Pedersen S., Physiology, Pharmacology and Pathophysiology of the pH Regulatory Transport Proteins NHE1 and NBCn1: Similarities, Differences, and Implications for Cancer Therapy, Current Pharmaceutical Design 2012; 18 (10) . https://dx.doi.org/10.2174/138161212799504830
DOI https://dx.doi.org/10.2174/138161212799504830 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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