Global translation response to brain ischemia, observed with neural PC12 cells

Dr. A. Zhdanov, Dr. R. Dmitriev and Prof. D. Papkovsky in collaboration with Dr. P. Baranov "LAPTI" group (University College Cork) and Moscow State University (Russia) have published joint research paper entitled "Oxygen and glucose deprivation induces widespread alterations in mRNA translation within 20 minutes" in Genome Biology open access journal. The team has focused efforts on novel technique - ribosome profiling - to determine immediate effects of cellular stress occurring during ischemia (oxygen and glucose deprivation) on global protein translation.
Some of the key findings of the study are:
-the indication of immediate cellular response, independent from well-known Hypoxia Inducible Factor (HIF) pathway;
-short-list of the key genes which translation is changed upon ischemia and
-widespread occurrence of non-canonical translation initiation that can lead to synthesis of "stress-induced" forms of proteins.
Collectively, this data should lead to development of better therapies of stroke, in brain as well as in other important human tissues such as heart.

The news are also appeared in Russian media.

This work also complements a number of recent publications of the team in the areas of hypoxia and ischemia effects on physiology of brain cells: the team members already reported that HIF pathway is downregulated in the the cells adapted to physiological low levels of oxygen (Zhdanov et al, 2012) and discovered epigenetic changes in cells experiencing ischemia in vitro (Dmitriev et al, 2015).

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