N-ethylmaleimide (NEM) Causes Aquaporin-2 Trafficking in the Renal Inner Medullary Collecting Duct by Direct Activation of Protein Kinase A
|Title:||N-ethylmaleimide (NEM) Causes Aquaporin-2 Trafficking in the Renal Inner Medullary Collecting Duct by Direct Activation of Protein Kinase A|
|Authors:||Shaw, Stephen; Marples, David|
|Publisher:||American Journal of Physiology: Renal Physiology|
|Date Published:||November 09, 2004|
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
Research using toad urinary bladders indicated another substance, N-ethylmaleimide (NEM) could affect transfer of AQP2 to the membrane. Shaw and Marples investigated the effects of NEM on AQP2 movement in mammalian cells by experimenting with laboratory rat cell cultures. They found that NEM is able to induce the movement of AQP2 from the rat cell interior to the cell membrane. Its ability to do this is dependent on the amount of NEM used in the laboratory cell culture, the most effective amount being 0.1 millimolar (mM). Just as with AVP, successful movement of AQP2 to the cell membrane initiated by NEM requires an intact cytoskeleton and the presence of PKA. The researchers reason that NEM stimulates AQP2 movement primarily by activating PKA directly, thus bypassing AVP receptors and adenylate cyclase.
The research team discovered that when both NEM and a maximal dose of AVP are applied to the cell culture, the amount of AQP2 moving to the membrane is increased. This suggests there are at least two molecular signaling paths involved in the efficient movement of AQP2 to the cell membrane. Shaw and Marples conclude that NEM’s ability to initiate AQP2 movement to the membrane via activation of PKA could be of value to researchers studying the cellular response of the kidney collecting duct to AVP. Potentially, such an approach might also be useful in patients with NDI.