Cellular swelling triggers the activation of Cl؊ channels (volume-sensitive outwardly rectifying (VSOR) Cl ؊ channels) in many cell types. Ensuing regulatory volume decrease has been considered the primary function of these channels. However, Cl ؊ channels, which share functional properties with volume-sensitive Cl ؊ channels, have been shown to be involved in other physiological processes, including cell proliferation and apoptosis, raising the question of their physiological roles and the signal transduction pathways involved in their activation. Here we report that exogenously applied H 2 O 2 elicited VSOR Cl ؊ channel activation. Furthermore, activation of these channels was found to be coupled to NAD(P)H oxidase activity. Also, epidermal growth factor, known to increase H 2 O 2 production, activated Cl ؊ channels with properties identical to swelling-sensitive Cl ؊ channels. It is concluded that NAD(P)H oxidasederived H 2 O 2 is the common signal transducing molecule that mediates the activation of these ubiquitously expressed anion channels under a variety of physiological conditions.
Gold nanorods used in therapy and diagnosis must be nontoxic and stable in biological media and should be specific for the target. The complete combination of these three factors has hindered the use of gold nanorods as carriers in biological and biomedical applications. In this study, we produced a conjugate of gold nanorods with the peptide CLPFFD that recognizes toxic β-amyloid aggregates present in Alzheimer's disease, demonstrates colloidal stability, maintains plasmonic properties, and shows no effects on cell viability in the SH-SY5Y cell line. Furthermore, the irradiation of β-amyloid in the presence of the conjugate with near-infrared region irradiation energy reduces the amyloidogenic process reducing also its cytotoxicity. The nanorods were synthesized following the seed-mediated method in cetyltrimethylammonium bromide (CTAB) and were conjugated with the N-terminal cysteine peptide, CLPFFD. The conjugate was exhaustively characterized using different techniques (Absorption spectroscopy, X-ray photoelectron spectroscopy, electron energy loss spectroscopy, and zeta potential). The effects on cell viability and cell penetration by transmission electron microscopy of the conjugate were evaluated. The chemisorption of the peptide on the surface of gold nanorods increases their stability and reduces their effects on cell viability.
Necrosis is associated with an increase in plasma membrane permeability, cell swelling, and loss of membrane integrity with subsequent release of cytoplasmic constituents. The transient receptor potential (TRP) 5 ion channel superfamily comprises a broad variety of cation-selective channels key to many physiological processes, including sensation, cell proliferation, and cell death (1, 2). TRPM4 is a Ca 2ϩ -activated and voltage-dependent monovalent cation selective channel corresponding to the melastatin subfamily of TRP channels (3).A distinct feature of TRPM4, as well as TRPM5 channels is that upon activation by intracellular Ca 2ϩ
The inclusion compound (IC) of cyclodextrin (CD) containing the antitumor drug Methotrexate (MTX) as a guest molecule was obtained to increase the solubility of MTX and decrease its inherent toxic effects in nonspecific cells. The IC was conjugated with gold nanoparticles (AuNPs), obtained by a chemical method, creating a ternary intelligent delivery system for MTX molecules, based on the plasmonic properties of the AuNPs. Irradiation of the ternary system, with a laser wavelength tunable with the corresponding surface plasmon of AuNPs, causes local energy dissipation, producing the controlled release of the guest from CD cavities. Finally, cell viability was evaluated using MTS assays for β-CD/MTX and AuNPs + β-CD/MTX samples, with and without irradiation, against HeLa tumor cells. The irradiated sample of the ternary system AuNPs + β-CD/MTX produced a diminution in cell viability attributed to the photothermal release of MTX.
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