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Bears and hibernation: new insights into metabolism in extreme conditions

Due to their ability to produce a potent inhibitor of protein degradation, hibernating bears do not lose muscle mass after long periods of hibernation.

This is the main conclusion of the study published in the journal Clinical Nutrition, directed by Professor Josep M. Argilés and co-written by Francisco J. López-Soriano, Gemma Fuster, Sílvia Busquets and Vanessa Almendro of the Cancer Research Group at the Biochemistry and Molecular Biology Department of the University of Barcelona (UB).

In the article, entitled «Antiproteolytic effects of plasma from hibernating bears: A new approach for muscle wasting therapy?», the team researches for the first time the physiological reasons for an effect that is well known to the scientific community – the fact that hibernating bears do not lose muscle tissue, only fat. In the experiment, the team studied the physiological response of muscle cells of laboratory rats grown with hibernating bear plasma outside the period of hibernation (from the Ursus arctos in the Aran Valley in the Pyrenees, a protected species since 1973). In the presence of hibernating bear plasma, the proteolytic rate in the rat muscle fell by 40%. «This suggests that the plasma of hibernating bears contains a factor that regulates protein breakdown, blocking this process in the organism», explains Argilés, Professor of Biochemistry and Molecular Biology at the Faculty of Biology.

Why study bears as a physiological model? Hibernation is a characteristic feature of the life cycle of this large mammal and, in the case of the Pyrenean bear, usually lasts from the second half of November until March or April. During hibernation, bears may go for up to three months without food or drink, and reduce their metabolism to adapt to these extreme conditions. What is more, bears have a relatively stable metabolism and conserve their body temperature in these situations.

In general, the destruction of muscle tissue (cachexia) is a sign of metabolic stress, and in humans is associated with pathologies such as cancer or AIDS or with long periods of malnutrition, immobilization and microgravity. The main channels of protein breakdown in cells are lysosomes and proteasomes, which are responsible for approximately 80% of the proteolytic activity. But the mechanisms of protein breakdown are still not well understood. «Compared with our knowledge of protein synthesis, we know very little about the processes of breakdown, especially about regulation. This possible inhibitory effect of hibernating bear plasma may regulate proteolysis in a natural way, which may have a series of implications for treatment», notes Argilés.

In 1993, the Cancer Research Group at the Biochemistry and Molecular Biology Department at the UB was the first to describe the ubiquitin-proteasome system, the proteolytic system involved in muscle mass loss in pathological situations. This system – an enzyme cascade – is the main cell pathway for protein turnover and also participates in key cellular processes such as the cell cycle, DNA repair, and so on. Years after this first discovery, the same team of scientists at the UB has again broken new ground in detecting a possible natural inhibitor of the cellular mechanisms involved in protein metabolism.

The experts are continuing their research to identify the factor that provokes the antiproteolytic effect, a discovery that would open up possibilities for future strategies for treating cachexia. «In many cases, the response to diseases can be found by studying nature», says Argilés, who is also organizing of the World Cachexia Congress to be held in 2009. Santiago Palazón, of the University of Barcelona, and Jesús Fernández, of Barcelona Zoo, also took part in the project published in Clinical Nutrition.

Rosa Martínez | alfa
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