H O induced astrocyte ATP release through lysosome exocytosi

H2O2 induced astrocyte ATP release through lysosome exocytosis. The LDH assay and electric microscope results indicated that the increase of extracellular ATP concentration was not due to the cell rupture, but the alternations in cell activities. In addition, when lysosome exocytosis was blocked by GPN, the increased extracellular ATP was inhibited. These data endorsed the original hypothesis that lysosomal exocytosis was involved in extracellular ATP increase after oxidative stress induced by H2O2 in a Ca2+-dependent pattern (Fig. 5A, B).
Conflict of interest statement
Introduction Over the last decades, genetic and biochemical analyses in the budding yeast Saccharomyces cerevisiae have identified the molecular machineries required for endocytosis and exocytosis. This work has unraveled the interplay of the protein components that drive these processes and has provided detailed insights into the regulatory network responsible for controlling exo- and endocytic activity [[1], [2], [3], [4]]. It is now well established that the basic mechanisms and characteristics of endocytosis and exocytosis are overall well conserved across the eukaryotic phyla. Among the few differences within eukaryotic cells the importance of the mitoxantrone cytoskeleton is noteworthy. While actin is essential for clathrin-mediated endocytosis in S. cerevisiae, its contribution to endocytosis in animal cells is less substantial [5]. In spite of this peculiarity, the high degree of conservation of endo- and exocytosis within the domain of eukaryotes justifies the prominent role of yeast as a model system for studying general aspects of the mechanisms of exo- and endocytosis. Classical membrane trafficking studies have focused on the requirement of different protein components and their specific functions. Membranes and their constitutive lipids have been instead regarded as a passive, structural component of the system without significant regulatory function. However, insights from other biological processes underscore the view that also membrane lipids are of regulatory significance [6]. It has been shown that membrane lipids contribute to the sensing of environmental parameters, such as temperature or the level of molecular oxygen [7,8], and that they are significantly involved in regulating the expression of numerous genes. The latter was best demonstrated in the context of the yeast OLE pathway [9,10] and the Upc2p-dependent SREBP-like pathway [11]. It has been shown that lipid-mediated regulatory functions are based on signal-mediating proteins (e.g. transcription activators). But there is also evidence that membrane lipids can directly regulate membrane-associated processes by altering viscosity, bending modules, thickness or packing density of lipid bilayers. For instance, membranes with a high degree of lipid saturation and high sterol content exhibit high packing density, resulting in low osmotic permeability coefficients (low water permeability) of the membrane [12]. Other studies have shown that including unsaturated fatty acids in phospholipid membranes lowered membrane thickness, which in turn lowered the energy needed for deformation, thus enhancing touch sensation and mechanoelectrical transduction in touch receptor neurons [13]. Besides the lipid content itself, temperature also modulates membrane fluidity, which can directly regulate vesicle fusion induced by divalent cations [14]. Physical membrane properties are mainly governed by the amount and chemical nature of membrane sterols, the unsaturation degree and length of lipid acyl chains as well as by the molecular lipid shape as e.g. specified by phospholipid head groups. Those lipid and membrane characteristics can be directly modulated by environmental factors that affect lipid biosynthesis, including the availability of molecular oxygen [[15], [16], [17]] or iron ions [18,19], lipid biosynthesis toxins [[20], [21], [22]], and chemical agents [23], or free lipids in the medium [24,25]. It is reasonable to assume that the external milieu could in this way modulate membrane-dependent cellular processes via changing basic physicochemical membrane parameters.