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Modulation of Ca2+ release by cyclic ADP-ribose (cADPR) in the scallop sarcoplasmic reticulum.
No full textMyelination increases chemical energy support to the axon without modifying the basic physicochemical mechanism of nerve conduction
No full textThe existence of different conductive patterns in unmyelinated and myelinated axons is uncertain. It seems that considering exclusively physical electrical phenomena may be an oversimplification. A novel interpretation of the mechanism of nerve conduction in myelinated nerves is proposed, to explain how the basic mechanism of nerve conduction has been adapted to myelinated conditions. The neurilemma would bear the voltage-gated channels and Na+/K+-ATPase in both unmyelinated and myelinated conditions, the only difference being the sheath wrapping it. The dramatic increase in conduction speed of the myelinated axons would essentially depend on an increment in ATP availability within the internode: myelin would be an aerobic ATP supplier to the axoplasm, through connexons. In fact, neurons rely on aerobic metabolism and on trophic support from oligodendrocytes, that do not normally duplicate after infancy in humans. Such comprehensive framework of nerve impulse propagation in axons may shed new light on the pathophysiology of nervous system disease in humans, seemingly strictly dependent on the viability of the pre-existing oligodendrocyte
Exosomes: Key tools for cancer liquid biopsy
No full textPrecision medicine is based on the identification of biomarkers of tumor development and progression. Liquid biopsy is at the forefront of the ability to gather diagnostic and prognostic information on tumors, as it can be noninvasively performed prior or during treatment. Liquid biopsy mostly utilizes circulating tumor cells, or free DNA, but also exosomes. The latter are nanovesicles secreted by most cell types, found in any body fluid that deliver
proteins, nucleic acids and lipids to nearby and distant cells with a unique homing ability. Exosomes function in signalling between the tumor microenvironment and the rest of the body, promoting metastasis, immune remodelling and drug resistance. Exosomes are emerging as a key tool in precision medicine for cancer liquid biopsy, as they efficiently preserve their biomarker cargo. Moreover, exosomes strongly resemble the parental cell, which can help in
assessing the oxidative and metabolic state of the donor cell. In this respect, exosomes represent one of the most promising new tools to fight cancer. This review will discuss the clinical applications of profiling exosomal proteins and lipids by high-throughput proteomics and metabolomics, and nucleic acids by next generation sequencing, as well as how this may allow cancer diagnosis, therapy response monitoring and recurrence detection
Essential role of Ca2+ -dependent phospholipase A2 in estradiol-induced lysosome activation. Am J Physiol Cell Physiol. 2002 Nov;283(5):C1461-8
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Cyclic ADP-ribose-dependent Ca2+ release is modulated by free [Ca2+] in the scallop sarcoplasmic reticulum
No full textBIOCHEMICAL-CHARACTERIZATION OF A PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE-SPECIFIC PHOSPHOLIPASE-C ACTIVITY IN GILLS AND DIGESTIVE GLAND OF THE MARINE MUSSEL MYTILUS-GALLOPROVINCIALIS LAM
No full textHigh Glucose Impairs Expression and Activation of MerTK in ARPE-19 Cells
No full textMerTK (Mer Tyrosine Kinase) is a cell surface receptor that regulates phagocytosis of pho-toreceptor outer segments (POS) in retinal pigment epithelial (RPE) cells. POS phagocytosis is im-paired in several pathologies, including diabetes. In this study, we investigate whether hyperglyce-mic conditions may affect MerTK expression and activation in ARPE-19 cells, a retinal pigment epithelial cellular model. ARPE-19 cells were cultured in standard (CTR) or high-glucose (HG) me-dium for 24 h. Then, we analyzed: mRNA levels and protein expression of MerTK and ADAM9, a protease that cleaves the extracellular region of MerTK; the amount of cleaved Mer (sMer); and the ability of GAS6, a MerTK ligand, to induce MerTK phosphorylation. Since HG reduces miR-126 levels, and ADAM9 is a target of miR-126, ARPE-19 cells were transfected with miR-126 inhibitor or mimic; then, we evaluated ADAM9 expression, sMer, and POS phagocytosis. We found that HG reduced expression and activation of MerTK. Contextually, HG increased expression of ADAM9 and the amount of sMer. Overexpression of miR-126 reduced levels of sMer and improved phago-cytosis in ARPE-19 cells cultured with HG. In this study, we demonstrate that HG compromises MerTK expression and activation in ARPE-19 cells. Our results suggest that HG up-regulates ADAM9 expression, leading to increased shedding of MerTK. The consequent rise in sMer coupled to reduced expression of MerTK impairs binding and internalization of POS in ARPE-19 cells
The hormetic effect of metformin: “less is more”?
No full textMetformin (MTF) is the first-line therapy for type 2 diabetes (T2DM). The euglycemic effect of MTF is due to the inhibition of hepatic glucose production. Literature reports that the principal molecular mechanism of MTF is the activation of 5′-AMP-activated protein kinase (AMPK) due to the decrement of ATP intracellular content consequent to the inhibition of Complex I, although this effect is obtained only at millimolar concentrations. Conversely, micromolar MTF seems to activate the mitochondrial electron transport chain, increasing ATP production and limiting oxidative stress. This evidence sustains the idea that MTF exerts a hormetic effect based on its concentration in the target tissue. Therefore, in this review we describe the effects of MTF on T2DM on the principal target organs, such as liver, gut, adipose tissue, endothelium, heart, and skeletal muscle. In particular, data indicate that all organs, except the gut, accumulate MTF in the micromolar range when administered in therapeutic doses, unmasking molecular mechanisms that do not depend on Complex I inhibition
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