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FCT Investigator reveals different effects of anti-inflammatory drug in the cell


The molecular effects of many pharmaceutical drugs are not fully understood. This is the nature of the problem that drives the research interests of Rune Matthiesen, a Danish FCT Investigator based at Instituto de Patologia e Imunolgia Molecular (University of Porto) and Instituto Nacional de Saúde Dr. Ricardo Jorge. Glucosamine supplements are a case in point. They are a popular and safe alternative to non-steroid anti-inflammatory drugs, for reducing pain, inflammation and maintaining healthy joints. Several studies have suggested that, besides providing pain relief for osteoarthritis patients, glucosamine may also protect against ischemia of the heart (reduced blood flow to the heart muscle) and help destroy cancer cells. Despite the promising results from many studies, a clear molecular role for glucosamine in treating disease has not yet been established, mainly do to the range of effects on cells and their molecules that the studies have uncovered.

In the latest issue of the journal Molecular and Cellular Proteomics, Rune and his team used novel technology to analyse state of art data on the proteins that are found in different compartments of certain cancer cells. The team discovered an increase in the transport of proteins to their appropriate destination upon glucosamine treatment. Furthermore, by comparing protein and gene expression, the team concluded that the glucosamine response acts on the control of the birth, folding, transport and degradation of proteins. This led to the interesting and somewhat surprising discovery that glucosamine can protect a specific cancer cell type in the laboratory against the anti-cancer drug Bortezomib, suggesting that drug treatment and diet needs further scientific scrutiny.

Their results give insight into the molecular mechanisms and pathways activated in the different compartments following glucosamine treatment, and could lead to the discovery of novel targets for the treatment of cardiovascular diseases, diabetes and cancer.

The team took a global approach to the problem, by looking both at the whole assortment of genes that are turned on by glucosamine (through so-called transcriptomics using DNA microarrays) and the changes in the proteins induced by glucosamine treatment of cells (so-called proteomics using mass spectrometry). All the raw data on the gene expression and protein changes collected in this study has been deposited in open-access databases, making it freely available to other researchers, across the world.

This study was fully funded by FCT, through Rune Matthiesen’s funding as a FCT Investigator, and several project grants and a post-doctoral fellowship; IPATIMUP is also a FCT-funded Associate Laboratory. Several research centres in Portugal contributed to the study: the Instituto Gulbenkian de Ciência (IGC, Lisbon) provided the microarray service, and the Instituto de Biologia Molecualr e Celular (IBMC, Porto) assisted in the flow cytometry experiments.