A two-faced enzyme: Dr Oxy and Mr Acid

GENEVA, Switzerland, January 7, 2000 - Generally, bleach makes you think about the last hair color change of a friend or the last wound cleaning of your youngest son. Believe it or not, when our cells produce energy they continuously generate this compound, a member of the reactive oxygen species family. They are harmful to the organism and lead to ageing, degenerative disease and cancer. But as usual, Nature is surprising. Our white blood cells, specially devoted to the destruction of bacterias, exhibits a particular protein, the NADPH oxidase. Guess what ? This enzyme generates reactive oxygen species& like bleach, a powerful anti-bacterial compound.

In its january 7 issue of the year 2000, the magazine Science presented the results published by a research group of the Faculty of Medicine in Geneva. They made in fact two discoveries during their investigation. The NADPH oxidase exhibited by the white blood cells were well known, but this was not the case for a new variant expressed in the intestine. This accounts for the first finding. Surprisingly, this enzyme, like certain movies, exists in a short and a long version : if the long one is able to produce bleach, it is not the case for the short one ! Our Geneva scientists were very intrigued by this dwarf version of NADPH oxidase and after several months of investigation they finally got the answer : it was a very efficient intracellular acid evacuation system, in other words, a proton channel. These channels play an essential role since they avoid that intestinal cells die due to an intracellular acid accumulation. Their existence was known, but the protein, until then, not identified. These scientist had thus the privilege to discover a new enzyme and to identify the first proton channel.

Who are they ? The main investigator is Botond Banfi, a medical student from the University of Budapest, who could spend a research fellowship at the biology of Ageing Laboratory of the Department of Geriatrics thanks to a grant from the Swiss National Science Foundation for the cooperation with east European countries. This study was supervised by Prof. Karl-Heinz Krause, head of the Biology of Ageing Laboratory and by Dr. Nicolas Demaurex at the Department of Physiology.

What could be the medical relevance of this newly described enzyme ? The precise physiological function of the intestinal NADPH oxidase remains to be defined. While the Geneva team suspects that the main role is the defense against bacteria in the intestine, competing group from the US who independentl identified the same protein, suspects it to be involved in cell growth and cancer. Both hypothesis might be right and Prof. Krause's group, in collaboration with the infectious disease and gastroenterology group, is now actively pursuing the potential role of the protein in intestinal infections, tumors, inflammation and ageing. The role of the intestinal H⁺ channel is clear : it protects cells from a deleterious acidification which occurs under many conditions of cellular stress like infection, hypoxia and extensive metabolic activity. By its capacity to evacuate the acid, the NADPH oxidase avoids cell suffering or even cell death. Because of their impact on cellular function and their accessibility to pharmacological agents, H⁺ channels might be in the future interesting