No abstract

BackgroundSuccinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models.ResultsWe found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophic-signaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases.ConclusionsThese results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12964-014-0078-2) contains supplementary material, which is available to authorized users.

The increasing interest in stem cell research is linked to the promise of developing treatments for many lifethreatening, debilitating diseases, and for cell replacement therapies. However, performing these therapeutic innovations with safety will only be possible when an accurate knowledge about the molecular signals that promote the desired cell fate is reached. Among these signals are transient changes in intracellular Ca2+ concentration [Ca2+]i. Acting as an intracellular messenger, Ca2+ has a key role in cell signaling pathways in various differentiation stages of stem cells. The aim of this chapter is to present a broad overview of various moments in which Ca2+-mediated signaling is essential for the maintenance of stem cells and for promoting their development and differentiation, also focusing on their therapeutic potential.

Resonance Raman spectroscopy with an energy tunable system is used to analyze the 600-1100 cm(-1) spectral region in single-wall carbon nanotubes. Sharp peaks are associated with the combination of zone folded optic and acoustic branches from 2D graphite. These combination modes exhibit a peculiar dependence on the excitation laser energy that is explained on the basis of a highly selective resonance process that considers phonons and electrons in low dimensional materials.

Graphene and its derivatives, due to a wide range of unique properties that they possess, can be used as starting material for the synthesis of useful nanocomplexes for innovative therapeutic strategies and biodiagnostics. Here, we summarize the latest progress in graphene and its derivatives and their potential applications for drug delivery, gene delivery, biosensor and tissue engineering. A simple comparison with carbon nanotubes uses in biomedicine is also presented. We also discuss their in vitro and in vivo toxicity and biocompatibility in three different life kingdoms (bacterial, mammalian and plant cells). All aspects of how graphene is internalized after in vivo administration or in vitro cell exposure were brought about, and explain how blood-brain barrier can be overlapped by graphene nanomaterials.