Cadmium (Cd), a category I human carcinogen, is a well-known widespread environmental pollutant. Chronic Cd exposure affects different organs and tissues, such as the central nervous system (CNS), and its deleterious effects can be linked to indirect reactive oxygen species (ROS) generation. Since Cd is predominantly present in +2 oxidation state, it can interplay with a plethora of channels and transporters in the cell membrane surface in order to enter the cells. Mitochondrial dysfunction, ROS production, glutathione depletion and lipid peroxidation are reviewed in order to better characterize the Cd-elicited molecular pathways. Furthermore, Cd effects on different CNS cell types have been highlighted to better elucidate its role in neurodegenerative disorders. Indeed, Cd can increase blood–brain barrier (BBB) permeability and promotes Cd entry that, in turn, stimulates pericytes in maintaining the BBB open. Once inside the CNS, Cd acts on glial cells (astrocytes, microglia, oligodendrocytes) triggering a pro-inflammatory cascade that accounts for the Cd deleterious effects and neurons inducing the destruction of synaptic branches.

L. Role for stress fiber contraction in surface tension development and stretch-activated channel regulation in C2C12 myoblasts. Am J Physiol Cell Physiol 295: C160 -C172, 2008. First published April 23, 2008 doi:10.1152/ajpcell.00014.2008.-Membrane-cytoskeleton interaction regulates transmembrane currents through stretchactivated channels (SACs); however, the mechanisms involved have not been tested in living cells. We combined atomic force microscopy, confocal immunofluorescence, and patch-clamp analysis to show that stress fibers (SFs) in C2C12 myoblasts behave as cables that, tensed by myosin II motor, activate SACs by modifying the topography and the viscoelastic (Young's modulus and hysteresis) and electrical passive (membrane capacitance, Cm) properties of the cell surface. Stimulation with sphingosine 1-phosphate to elicit SF formation, the inhibition of Rho-dependent SF formation by Y-27632 and of myosin II-driven SF contraction by blebbistatin, showed that not SF polymerization alone but the generation of tensional forces by SF contraction were involved in the stiffness response of the cell surface. Notably, this event was associated with a significant reduction in the amplitude of the cytoskeleton-mediated corrugations in the cell surface topography, suggesting a contribution of SF contraction to plasma membrane stretching. Moreover, Cm, used as an index of cell surface area, showed a linear inverse relationship with cell stiffness, indicating participation of the actin cytoskeleton in plasma membrane remodeling and the ability of SF formation to cause internalization of plasma membrane patches to reduce Cm and increase membrane tension. SF contraction also increased hysteresis. Together, these data provide the first experimental evidence for a crucial role of SF contraction in SAC activation. The related changes in cell viscosity may prevent SAC from abnormal activation. actin remodeling; atomic force microscopy, Young's modulus; membrane capacitance; hysteresis STRETCH-ACTIVATED CHANNELS (SACs) are voltage-independent nonselective ion channels localized on the plasma membrane, where they play an important role as mechanoreceptors (33). These channels, in fact, are gated by tension developed within the lipid bilayer (25) and transduce the mechanical stimulus into increased cation current and Ca 2ϩ influx, thus converting electrical signals into biochemical events involved in the coordination of numerous cellular processes, ranging from cell volume regulation, membrane potential control, and muscle cell contraction to regulation of gene expression and cell differentiation (8, 9, 28). The analysis of mechanotransduction has been focused on the identification of critical molecules and cellular components, such as integrins, focal adhesions, cadherins, gap junctions, and cytoskeleton, which, modulating cell-cell and cell-matrix interactions, contribute to the mechanosensitivity and promote SAC opening (18). However, there is increasing evidence suggesting that actin cytoskeleton reorganization may also...

No abstract

No abstract

Growing evidence has shown the promise of mesenchymal stromal cells (MSCs) for the treatment of cutaneous wound healing. We have previously demonstrated that MSCs seeded on an artificial dermal matrix, Integra (Integra Lifesciences Corp., Plainsboro, NJ) enriched with platelet-rich plasma (Ematrix) have enhanced proliferative potential in vitro as compared with those cultured on the scaffold alone. In this study, we extended the experimentation by evaluating the efficacy of the MSCs seeded scaffolds in the healing of skin wounds in an animal model in vivo. It was found that the presence of MSCs within the scaffolds greatly ameliorated the quality of regenerated skin, reduced collagen deposition, enhanced reepithelization, increased neo-angiogenesis, and promoted a greater return of hair follicles and sebaceous glands. The mechanisms involved in these beneficial effects were likely related to the ability of MSCs to release paracrine factors modulating the wound healing response. MSC-seeded scaffolds, in fact, up-regulated matrix metalloproteinase 9 expression in the extracellular matrix and enhanced the recruitment of endogenous progenitors during tissue repair. In conclusion, the results of this study provide evidence that the treatment with MSC-seeded scaffolds of cutaneous wounds contributes to the recreation of a suitable microenvironment for promoting tissue repair/regeneration at the implantation sites.Bone marrow-derived mesenchymal stromal cells (MSCs) generate great expectation in the field of regenerative medicine due to the easy isolation and expansion, unique antiinflammatory and immune-modulatory properties, and their potential multipotency.