5/27/2023 0 Comments Mr contrast agents![]() ![]() The two main purposes of this work were: (i) to critically consider the use of thermodynamic parameters of activation for elucidating the drug release mechanism from hydroxypropyl methylcellulose (HPMC) matrices, and (ii) to examine the effect of neutral (pH 6) and acidic (pH 2) media on the release mechanism. These findings show the potential susceptibility of the CNS to weak SMF exposure and have implications for the design of novel strategies for the treatment and/or prevention of neurodegenerative diseases. Our findings demonstrating altered Ca 2+-influx in response to thapsigargin stimulation in SMF-exposed cortical neurons, along with enhanced inhibition of KCl-induced Ca 2+-influx through Ca v1.2 channels and enhanced expression of Ca v1.2 and Ca v1.3 channels, allude to the involvement of voltage- and store-operated Ca 2+ channels in various aspects of the protective effect exerted by SMFs. Using the L-type voltage-gated Ca 2+ channel inhibitor nifedipine, which is selective to Ca 2+ influx through Ca v1.2, we found that the anti-apoptotic effect of SMFs was mediated by Ca 2+ influx through these channels. Primary cortical neurons exposed to SMF (50 G) for 7 days exhibited a 57.1 ± 6.3% decrease in the percentage of cells undergoing apoptosis induced by etoposide (12 μM), accompanied by a marked decrease in the expression of the pro-apoptotic markers: cleaved poly ADP ribose polymerase-1, cleaved caspase-3, active caspase-9 and the phospho-histone H2A variant (Ser139) by 41.0 ± 5.0%, 81.2 ± 5.0%, 72.9 ± 6.4%, 42.75 ± 2.9%, respectively, and by a 57.2 ± 1.0% decrease in the extent of mitochondrial membrane potential collapse. We show that weak SMF exposure interferes with the apoptotic programing in rat primary cortical and hippocampal neurons, thereby providing protection against etoposide-induced apoptosis in a dose- and time-dependent manner. In this study, we examine the effect of SMFs on neuronal survival in primary cortical and hippocampal neurons that constitute a suitable experimental system for modeling the neurodegenerative state in vitro. Previous studies describing the effect of SMFs on apoptotic cell death in several non-neuronal cell lines, emphasize the importance of such a potential modulation in the case of neurodegenerative disorders, where apoptosis constitutes a major route via which neurons degenerate and die. Low intensity static magnetic fields (SMFs) interact with various biological tissues including the CNS, thereby affecting key biological processes such as gene expression, cell proliferation and differentiation, as well as apoptosis. Together, our study shows how maturation of active catalase can be influenced by NO, S-nitrosylated GAPDH, and thioredoxin-1, and how maturation may become compromised in inflammatory conditions such as asthma. In a mouse model of allergic inflammatory asthma, we found that lungs from allergen-challenged mice contained a greater percentage of dimeric catalase relative to tetrameric catalase in the unchallenged control, suggesting that the mechanisms described here are in play in the allergic asthma model. Moreover, the NO sensitivity of catalase maturation could be altered up or down by manipulating the cellular expression level or activity of thioredoxin-1, a known protein-SNO denitrosylase enzyme. We also found that GAPDH plays a key role in mediating these NO effects on the structure and activity of catalase. The NO inhibition in catalase heme incorporation was associated with defective oligomerization of catalase, such that inactive catalase monomers and dimers accumulated in place of the mature tetrameric enzyme. We found that NO attenuates heme insertion into catalase in both short-term and long-term incubations. However, the possible impact of NO in relation to the maturation of active catalase, including its heme acquisition and tetramer formation, has not been investigated. Multiple factors including nitric oxide (NO) have been shown to attenuate its activity. Catalase is a tetrameric heme-containing enzyme with essential antioxidant functions in biology.
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