scholarly journals Protection of Mycobacterium tuberculosis from Reactive Oxygen Species Conferred by the mel2 Locus Impacts Persistence and Dissemination

2009 ◽  
Vol 77 (6) ◽  
pp. 2557-2567 ◽  
Author(s):  
Suat L. G. Cirillo ◽  
Selvakumar Subbian ◽  
Bing Chen ◽  
Torin R. Weisbrod ◽  
William R. Jacobs ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mycobacterium Tuberculosis ◽  
Bacterial Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Wild Type ◽  
Primary Mechanism ◽  
Insight Into ◽  
Increased Susceptibility

ABSTRACT Persistence of Mycobacterium tuberculosis in humans represents a major roadblock to elimination of tuberculosis. We describe identification of a locus in M. tuberculosis, mel2, that displays similarity to bacterial bioluminescent loci and plays an important role during persistence in mice. We constructed a deletion of the mel2 locus and found that the mutant displays increased susceptibility to reactive oxygen species (ROS). Upon infection of mice by aerosol the mutant grows normally until the persistent stage, where it does not persist as well as wild type. Histopathological analyses show that infection with the mel2 mutant results in reduced pathology and both CFU and histopathology indicate that dissemination of the mel2 mutant to the spleen is delayed. These data along with growth in activated macrophages and infection of Phox−/− and iNOS−/− mice and bone marrow-derived macrophages suggest that the primary mechanism by which mel2 affects pathogenesis is through its ability to confer resistance to ROS. These studies provide the first insight into the mechanism of action for this novel class of genes that are related to bioluminescence genes. The role of mel2 in resistance to ROS is important for persistence and dissemination of M. tuberculosis and suggests that homologues in other bacterial species are likely to play a role in pathogenesis.

scholarly journals Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Noah C. Jenkins ◽  
Douglas Grossman
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Cell Types ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Potential Alternative ◽  
Oxidative Insult ◽  
Increased Susceptibility

We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS) than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS) may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.

Role of reactive oxygen species and antioxidants in periodontal disease

2021 ◽  
pp. 1-16
Author(s):  
Harish M. Saluja ◽  
Shivani Sachdeva ◽  
Amit Mani
Keyword(s):  
Reactive Oxygen Species ◽  
Periodontal Disease ◽  
Bacterial Species ◽  
Reactive Oxygen ◽  
Epidemiological Studies ◽  
Oxygen Species ◽  
Tissue Destruction ◽  
Tnf Α ◽  
Harmful Effects

Recent epidemiological studies reveal that more than two-third of the world’s population suffers from one of the chronic forms of periodontal disease. The primary etiological agent of this inflammatory disease is a polymicrobial complex, predominantly Gram negative anaerobic or facultative bacteria within the sub-gingival biofilm. These bacterial species initiate the production of various cytokines such as interleukin-8 and TNF-α, further causing an increase in number and activity of polymorphonucleocytes (PMN) along with these cytokines, PMNs also produce reactive oxygen species (ROS) superoxide via the respiratory burst mechanism as the part of the defence response to infection. ROS just like the interleukins have deleterious effects on tissue cells when produced in excess. To counter the harmful effects of ROS, human body has its own defence mechanisms to eliminate them as soon as they are formed. The aim of this review is to focus on the role of different free radicals, ROS, and antioxidants in the pathophysiology of periodontal tissue destruction.

MYB134-RNAi poplar plants show reduced tannin synthesis in leaves but not roots, and increased susceptibility to oxidative stress

2020 ◽  
Vol 71 (20) ◽  
pp. 6601-6611
Author(s):  
Geraldine Gourlay ◽  
Dawei Ma ◽  
Axel Schmidt ◽  
C Peter Constabel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Condensed Tannin ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Rna Seq ◽  
Wild Type ◽  
And Control ◽  
Increased Susceptibility

Abstract The importance of the poplar MYB134 gene in controlling condensed tannin (CT) biosynthesis was tested by suppressing its expression using RNA interference (RNAi). MYB134-RNAi plants grew normally but showed reduced accumulation of stress-induced CTs in leaves. RNA-seq analysis indicated that flavonoid- and CT-related genes, as well as additional CT regulators, were strongly and specifically down-regulated by MYB134 suppression. This confirmed that the primary MYB134 target is the leaf flavonoid and CT pathway. Root CT accumulation was not impacted by MYB suppression, suggesting that additional CT regulators are active in roots and emphasizing the complexity of the regulation of CTs in poplar. To test the effect of CT down-regulation on oxidative stress resistance, leaves of MYB134-RNAi and control plants were exposed to the reactive oxygen species generator methyl viologen. MYB134-RNAi leaves sustained significantly more photosystem II damage, as seen in reduced chlorophyll fluorescence, compared with wild-type leaves. MYB134-RNAi leaves also contained more hydrogen peroxide, a reactive oxygen species, compared with the wild type. Our data thus corroborate the hypothesis that CT can act as an antioxidant in vivo and protect against oxidative stress. Overall, MYB134 was shown to be a central player in the regulation of CT synthesis in leaves.

Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species

2007 ◽  
Vol 293 (5) ◽  
pp. E1311-E1319 ◽  
Author(s):  
Edward R. Duncan ◽  
Simon J. Walker ◽  
Vivienne A. Ezzat ◽  
Stephen B. Wheatcroft ◽  
Jian-Mei Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Wild Type

Insulin resistance is well established as an independent risk factor for the development of type 2 diabetes and cardiovascular atherosclerosis. Most studies have examined atherogenesis in models of severe insulin resistance or diabetes. However, by the time of diagnosis, individuals with type 2 diabetes already demonstrate a significant atheroma burden. Furthermore, recent studies suggest that, even in adolescence, insulin resistance is a progressive disorder that increases cardiovascular risk. In the present report, we studied early mechanisms of reduction in the bioavailability of the antiatheroscerotic molecule nitric oxide (NO) in very mild insulin resistance. Mice with haploinsufficiency for the insulin receptor (IRKO) are a model of mild insulin resistance with preserved glycemic control. We previously demonstrated that 2-mo-old (Young) IRKO mice have preserved vasorelaxation responses to ACh. This remained the case at 4 mo of age. However, by 6 mo, despite no significant deterioration in glucose homeostasis (Adult), IRKO mice had marked blunting of ACh-mediated vasorelaxation [IRKO maximum contraction response (Emax) 66 ± 5% vs. wild type 87 ± 4%, P < 0.01]. Despite the endothelial dysfunction demonstrated, aortic endothelial nitric oxide synthase (eNOS) mRNA levels were similar in Adult IRKO and wild-type mice, and, interestingly, aortic eNOS protein levels were increased, suggesting a compensatory upregulation in the IRKO. We then examined the potential role of reactive oxygen species in mediating early endothelial dysfunction. The superoxide dismutase mimetic Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) restored ACh relaxation responses in the Adult IRKO (Emax to ACh with MnTMPyP 85 ± 5%). Dihydroethidium fluorescence of aortas and isolated coronary microvascular endothelial cells confirmed a substantial increase in endothelium-derived reactive oxygen species in IRKO mice. These data demonstrate that mild insulin resistance is a potent substrate for accelerated endothelial dysfunction and support a role for endothelial cell superoxide production as a mechanism underlying the early reduction in NO bioavailability.

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