Monday, January 16, 2012

Sugar metabolism explains how cells prevent death

Cells need a constant supply of oxygen to survive. Additionally, if they are not fed with sugar in time, it will also result in premature death. In nature, animals can never be sure when their next meal is. That is why cells are able to prepare themselves for harsh times, in which food is scarce. They can be trained to withstand low glucose, which is the form of sugar that is used by cells. Likewise, cells exposed to low oxygen can also be trained to survive in lower concentrations. It was long thought the two training mechanisms were not the same, but scientists from Germany and Canada have actually shown they are connected. We may use this newfound information to prevent cells from dying. Especially the ones that are hard to grow back, such as brain cells.

Experiments on the survival mechanisms were performed with nerve cells, which are often permanently damaged in the case of oxygen deprivation, and therefore would benefit a lot from new therapies. An example is stroke: if a part of the brain does not receive blood, which supplies it with oxygen and nutrients, for a while it will result in permanent loss of function. Putting the cells in low oxygen conditions revealed that their survival depends on an enzyme that is actually involved with sugar metabolism, linking oxygen and glucose regulation, which are basic and extremely important cellular processes.

The enzyme that seems to play such a pivotal role in survival is called hexokinase II. Its role in glucose metabolism is to make sure the cell can actually use sugar molecules as an energy source. Oddly enough, it is also activated in response to a lower-than-healthy concentration of oxygen. According to the scientists, it plays a protective role in the cell in situations of low oxygen concentration. When it cannot assert its effects, the cell will instead turn into suicide mode and kill itself.

It is especially interesting to study the role of hexokinase II in stroke, which is characterized by a sudden loss of oxygen, sometimes temporarily, in a part of the brain. Nerves suffer damage that is often impossible to repair. After the initial damage caused by the abrupt loss of oxygen, many cells kill themselves over time, because the lower supply of oxygen and nutrients is not enough to sustain themselves. This could theoretically be countered by cranking up the activity of hexokinase II, buying us more time to restore the oxygen and nutrient flow to the damaged part of the brain.

Other diseases
It does not stop at stroke. Tumours are always looking for ways to utilize more glucose in order to provide them with the required energy for excessive growth. They often find themselves in situations of low oxygen as well, because it is harder for blood vessels to reach every cell in fast-growing structures. Hexokinase II is implied in various cancers, which makes it, in combination with the newfound knowledge, a suitable target for the development of anti-cancer drugs. Additionally, the glucose and oxygen regulation system plays a role during infection, which highlights the numerous possibilities that hexokinase II pathway provides for clinical use. It is perhaps not very surprising, because oxygen and glucose regulation are among the most important processes in a cell.

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