Effects of probiotic bacterial quorum sensing peptides on lifespan of cerebellum neuron cells

BONGIOVANNI BETTINA; GRAU ROBERTO

Buzios, Brasil

Congreso; I Congreso IBRO/LARC de Neurociencias de América Latina, Caribe y Península Ibérica; 2008

IBRO/LARC

Quorum sensing (QS) provides bacteria with the ability to communicate and change behaviors across kingdoms. While many studies have focused on QS of pathogenic bacteria, the effects of QS from beneficial probiotic bacteria on eukaryotic cells have received poor attention. In our laboratory we are interested on QS of a particular probiotic intestinal bacterium (Bacillus subtilis Natto) that produces several beneficial effects on human health. B. subtilis produces up to eight different pentapeptides (Phr) with QS activity that would be involved in the healthy interaction with human cells. In this respect, we and others reported a stimulatory effect of B. subtilis on innate immunity, galectin expression and a Phr-mediated activation of cytoprotective proteins in intestinal epithelial cells. Because of the known effects of probiotic bacteria on the immune system, and the connection of this system with the nerve system, we were intrigued to explore the effect of QS on neural cells. In this communication we report the effects of B. subtilis QS peptides on lifespan and resistance to oxidative stress of cultures of neurons isolated from rat cerebellum. Physiological concentrations of PhrA and PhrC QS peptides produced a dose-dependent increase on the expression (measured by RT-PCR) of the anti-aging gene in neuron cultures. Increased levels of Sirtuin 7 would result in prolonged neural survival and enhanced stress-resistance, a hypothesis that we confirmed by immunocytochemistry studies that showed that, in the presence of Phr peptides, the levels of proteasome-related ubiquitin (a small 76 residue protein involved in intracellular degradation of miss-folded proteins) were decreased. Furthermore, rat neurons showed increased survival and decreased oxidative damage, evidenced by labeling with the fluorescent markers propidium iodide and SYTO 9 dye, when cultured in the presence of either PhrA or PhrC. These results suggest a key and previously unknown role of QS molecules on nerve system oxidative protection and lifespan, effects that would be the target for future developments of therapeutic molecules to treat aging-related neurodegenerative diseases.