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Dam Rose posted an update 6 months ago
Human DNA polymerase γ (POLG) is a mitochondria-specific replicative DNA polymerase consisting of a single catalytic subunit, POLGα, and a dimeric accessory subunit, POLGβ. To gain a deeper understanding of the role of POLGβ, we knocked out this protein in cultured human cybrid cells and established numerous knockout clones. POLGβ-knockout clones presented a clear phenotype of mitochondrial DNA loss, indicating that POLGβ is necessary for mitochondrial DNA replication. Moreover, POLGβ-knockout cells showed a severe decrease in POLGα levels and acute suppression of POLGβ expression efficiently down-regulated POLGα levels. These results suggest that, in addition to its role as the processivity factor of POLG, POLGβ acts as a POLGα stabilizer, an important role for POLGβ in mitochondrial DNA maintenance.Mitochondria is a dynamic organelle of the cell that can regulate and maintain cellular ATP level, ROS production, calcium signaling and immune response. In order to retain their shape and distribution, mitochondria go through coordinated cycles of fission and fusion. Further, dysfunctional mitochondria are selectively eliminated from the cell via mitophagy to synchronize mitochondrial quality control and cellular homeostasis. In addition, mitochondria when in close proximity with the endoplasmic reticulum can alter the signaling pathways and some recent findings also reveal a direct correlation between the mitochondrial localization in the cell to the immune response elicited against the invading pathogen. These modulations in the mitochondrial network are collectively termed as ‘mitochondrial dynamics’. Diverse bacteria, virus and parasitic pathogens upon infecting a cell can alter the host mitochondrial dynamics in favor of their multiplication and this in turn can be a major determinant of the disease outcome. Pharmacological perturbations in these pathways thus could lead to generation of additional therapeutic opportunities. This review will focus on the pathogenic modulation of the host mitochondrial dynamics, specifically during the bacterial infections and describes how dysregulated mitochondrial dynamics facilitates the pathogen’s ability to establish efficient infection.Th17 cells have been implicated in the pathogenesis of numerous inflammatory and autoimmune conditions. At the ocular surface, Th17 cells have been identified as key effector cells in chronic ocular surface disease. Evidence from murine studies indicates that following differentiation and expansion, Th17 cells migrate from the lymphoid tissues to the eye, where they release inflammatory cytokines including, but not limited to, their hallmark cytokine IL-17A. As the acute phase subsides, a population of long-lived memory Th17 cells persist, which predispose hosts both to chronic inflammation and severe exacerbations of disease; of great interest is the small subset of Th17/1 cells that secrete both IL-17A and IFN-γ in acute-on-chronic disease exacerbation. Over the past decade, substantial progress has been made in deciphering how Th17 cells interact with the immune and neuroimmune pathways that mediate chronic ocular surface disease. Here, we review (i) the evidence for Th17 immunity in chronic ocular surface disease, (ii) regulatory mechanisms that constrain the Th17 immune response, and (iii) novel therapeutic strategies targeting Th17 cells.Multidrug-resistance protein-1 facilitates the efflux of arsenic conjugated with reduced glutathione nonetheless; the relation between Mrp-1 ATPase activity and cellular GSH levels is contentious. To study this, Mrp-1-ATPase activity was measured in 5 μM arsenic trioxide exposed zebrafish hepatocytes (ZFH) and correlated with intracellular GSH levels. Alongside, mrp-1 gene expression as well as Mrp-1 protein level was also monitored. Diverse mode of Mrp-1 inhibition was reflected from differential level of Km and Vmax of Mrp-1 at different time points. 3 h post-arsenic treatment demonstrated non-competitive inhibition. At 6 h, there was significant increase in Km and ZFH death, suggesting reduced binding affinity of Mrp-1 for ATP. Increased caspase-9-cytochromeC-ATP levels (putative apoptosome), reinforced ZFH apoptosis. The increase in Vmax coupled with reduced substrate affinity of Mrp-1 suggests malfunctioning in arsenic- tolerance mechanisms. We posit the triggering glutathione level regulate arsenic tolerance in ZFH. Irreversible impairment of ATP binding to Mrp-1 culminates in arsenic-induced ZFH apoptosis.In this study, we report the antioxidant and antitoxic potential of chemically synthesized 4-oxo-2-phenyl-4H-chromene-7,8-diyl bis((1-amino-2-hydroxypropyl)carbamate) (DHF-BAHPC) compound using in vitro and in vivo assays. The DHF-BAHPC was synthesized by linking 7,8-Dihydroxyflavone (DHF) with two molecules of Fmoc-threonine and characterized by Ultraviolet-visible spectroscopy (UV-vis), Fourier-transform infrared spectroscopy (FT-IR), 1H NMR, 13C NMR and Mass spectrometry (MS). In vitro, antioxidant assay results revealed that DHF-BAHPC has a dose-dependent radical scavenging potential towards DPPH, ABTS, FRAP and H2O2 radicals with an IC50 range of 15.45, 66.27, 25.71, 4.375 μg/mL, respectively. Furthermore DHF-BAHPC treatment significantly altered cadmium (Cd) intoxicated zebrafish embryos by rescuing the developmental changes associated with severe histological and reduced the level of defensive antioxidant activities (SOD, CAT, GPx and GST). The overall results of the present study represented that DHF-BAHPC may be used as a potential drug in redox-based therapeutics.Catalase, an important antioxidant enzyme, is known to have a neuroprotective role against neurodegenerative disorder. Earlier study has focussed on benzothiazole-triazole hybrid molecules that are larger in size and molecular weight and inhibit the amyloid β (Aβ)-catalase interaction thus aid in neuroprotection. Here we have synthesized the novel benzothiazole molecules with low molecular weight using One-pot methodology and assayed the neuroprotective effects of the synthesized compounds in the U87 MG cell line under H2O2 induced stressed condition and compared with other cell lines such as breast cancer (MCF-7) and macrophage (RAW-264.7) using cell viability assay. SC79 These analogs were found to enhance the neuronal cell viability and protect neuronal cells from the ROS mediated neuronal damage induced by H2O2. Furthermore, compounds 6a, 6b, 6c, 6d, and 7a modulate catalase and enhanced the catalase activity up to 90 % during the H2O2 exposure in the U87MG cell line. These analogs (6a, 6b, 6c and 6d) have exhibited strong binding energies of -7.
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