miércoles, 13 de junio de 2012

RV: Body Clock Research Keeps Ticking On

Fuente: University of Leicester - Press Releases
Expuesto el: martes, 12 de junio de 2012 13:00
Autor: pt91
Asunto: Body Clock Research Keeps Ticking On

 

Published by University of Leicester on 12 June 2012

Researchers have found that a recently-discovered process that makes our body clocks tick dates back 2.5 million years and is as old as the oxygen in the Earth's atmosphere.

Previous research by scientists from the University of Leicester and colleagues from Cambridge discovered a 24 hour cycle in the Peroxiredoxin protein in mammalian liver cells.  Peroxiredoxin is a protein that mops up the unwanted cellular side-effects of breathing oxygen, free radicals and hydrogen peroxide.  However, internal body clocks were thought to be run by the TTO (transcription-translation oscillator) whereby genes are transcribed and translated into proteins and the proteins feedback and inhibit their own genes, the so-called ‘negative-feedback cycle’). Surprisingly, a specific biochemical oscillation in Peroxiredoxin depends only on translation, so the protein cycles "by itself" without gene transcription. 

In their new paper, published in the acclaimed Nature science journal, University of Leicester's Professor Kyriacou and his post-doctoral assistant Edward Green collaborated with researchers around the globe to trace the evolution of this protein.  They observed that this translational Peroxiredoxin cycle was found in every life-form, from bacteria to insects, mammals and plants, revealing that it had been around for at least 2.5 million years.

The TTO process was bolted on to the translational cycle about 1 billion years ago and indeed the two cycles are interlocked with each other, so a change in the TTO generates a change in the timing of the Peroxiredoxin cycle.

The Peroxiredoxin cycle evolved around the time that the Earth experienced the Great Oxygenation Event, when more oxygen was created within the planet's atmosphere for the first time, initially by photosynthetic bacteria.

The discovery is important because it further explains why we and other organisms that live on Earth's have a 24-hour circadian (Latin for ‘about a day’) cycle. The circadian clock can be affected by certain factors, such as light, temperature and eating or drinking habits. Without a regular cycle, we can suffer from sleep disorders, metabolic problems such as obesity, depression and cardiovascular disorders - in fact, most of us have suffered jet lag at one time or another because of a disrupted rhythm.

Professor Kyriacou states: "The original finding of a Peroxiredoxin cycle came from a study we performed on liver cells in collaboration with our Cambridge colleagues Dr Mick Hastings and Dr Kathryn Lilley (the latter used to be in the Biochemistry Department at Leicester).  However, Akhilesh Reddy, our Cambridge researcher on that project (incidentally, a neurologist who comes from Leicester) was smart enough to realise that Peroxiredoxins are also important components of red blood cells, that have no nucleus, and so gene transcription and thus the TTO  cannot account for the cycle.  He showed this in two beautiful Nature papers last year. The current paper extends this Peroxiredoxin mechanism to all life forms and shows how the Peroxiredoxin cycle is interconnected with the TTO, which evolved much later.  It is a very important finding in the field and we were happy that we could contribute to Ak’s study in this way."

Thanks to Professor Kyriacou and  Ed Green who performed the fruit fly work in this study, as well as their national and international collaborators, this new finding takes one more step towards understanding what makes us - and all other life forms - tick.

Their research paper “Peroxiredoxins are conserved markers of circadian rhythms” can be found on www.nature.com. Funding was provided by the Wellcome Trust, the European Research Council, the EMBO Young Investigators Programme, as well as by the MRC Centre for Obesity and Related Metabolic Disorders. The study was supported by the National Institute for Health Research Cambridge Biomedical Research Centre.


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