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Abnormal membrane protein causes hypertension
Issue date: 12/6/07
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Until the present study, it was unclear which type of antiporter was involved in SLC.
Many scientists viewed SLC as a modification of another electrolyte-transport process that exchanges protons and sodium ions and is used to regulate a cell's pH. (The antiporter in that case is called the sodium-hydrogen antiporter or NHA.)
Lithium ions, the theory went, would simply replace protons in the exchange with sodium.
More recent evidence, however, suggested that SLC and sodium-hydrogen transport don't actually involve the same antiporter protein.
The drug amiloride, which is known to act on certain antiporters, blocks sodium-hydrogen transport but not SLC.
The objective of Rao and her team, then, was to find an amiloride-insensitive antiporter protein.
To do so, they analyzed over 550 genes whose codes they conjectured could produce the desired protein.
They came across two previously undescribed genes, now called NHA1 and NHA2, which bore striking similarities to sodium-hydrogen exchangers already identified in E. coli.
What's more, the team found that versions of NHA1 and NHA2 exist in all animals, including nematodes, flies, puffer fish and mice.
The researchers hypothesized that the human version of NHA2 was the antiporter responsible for SLC in our bodies, and they uncovered some convincing evidence to that end.
By inserting the NHA2 gene into blank yeast cells, they observed that the protein it produced resided in the plasma membrane (as any antiporter is obliged to do) and, more importantly, that its function was entirely insensitive to amiloride.
In addition, they detected the presence of human NHA2 in red blood cells, where increased SLC is associated with essential hypertension.
Nonetheless, the NHA genes are still considered "candidate" genes for essential hypertension.
Many points remain unclear. Are there simply more NHA2 proteins in people with the disorder, or are those proteins merely overactive in hypertension?
Understanding genetics and molecular biology could also help answer questions about lifestyle. What effects do behavior and diet have on SLC activity? The country's blood pressure continues to rise, but only time will tell.
Many scientists viewed SLC as a modification of another electrolyte-transport process that exchanges protons and sodium ions and is used to regulate a cell's pH. (The antiporter in that case is called the sodium-hydrogen antiporter or NHA.)
Lithium ions, the theory went, would simply replace protons in the exchange with sodium.
More recent evidence, however, suggested that SLC and sodium-hydrogen transport don't actually involve the same antiporter protein.
The drug amiloride, which is known to act on certain antiporters, blocks sodium-hydrogen transport but not SLC.
The objective of Rao and her team, then, was to find an amiloride-insensitive antiporter protein.
To do so, they analyzed over 550 genes whose codes they conjectured could produce the desired protein.
They came across two previously undescribed genes, now called NHA1 and NHA2, which bore striking similarities to sodium-hydrogen exchangers already identified in E. coli.
What's more, the team found that versions of NHA1 and NHA2 exist in all animals, including nematodes, flies, puffer fish and mice.
The researchers hypothesized that the human version of NHA2 was the antiporter responsible for SLC in our bodies, and they uncovered some convincing evidence to that end.
By inserting the NHA2 gene into blank yeast cells, they observed that the protein it produced resided in the plasma membrane (as any antiporter is obliged to do) and, more importantly, that its function was entirely insensitive to amiloride.
In addition, they detected the presence of human NHA2 in red blood cells, where increased SLC is associated with essential hypertension.
Nonetheless, the NHA genes are still considered "candidate" genes for essential hypertension.
Many points remain unclear. Are there simply more NHA2 proteins in people with the disorder, or are those proteins merely overactive in hypertension?
Understanding genetics and molecular biology could also help answer questions about lifestyle. What effects do behavior and diet have on SLC activity? The country's blood pressure continues to rise, but only time will tell.
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