Mitochondrial permeability transition pore is involved in oxidative burst and NETosis of human neutrophils

Publication date: Available online 8 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Nina Vorobjeva, Ivan Galkin, Olga Pletjushkina, Sergei Golyshev, Roman Zinovkin, Anastasia Prikhodko, Vladimir Pinegin, Irina Kondratenko, Boris Pinegin, Boris ChernyakAbstractNeutrophils release neutrophil extracellular traps (NETs) in response to numerous pathogenic microbes as the last suicidal resource (NETosis) in the fight against infection. Apart from the host defense function, NETs play an essential role in the pathogenesis of various autoimmune and inflammatory diseases. Therefore, understanding the molecular mechanisms of NETosis is important for regulating aberrant NET release. The initiation of NETosis after the recognition of pathogens by specific receptors is mediated by an increase in intracellular Ca2+ concentration, therefore, the use of Ca2+ ionophore A23187 can be considered a semi-physiological model of NETosis. Induction of NETosis by various stimuli depends on reactive oxygen species (ROS) produced by NADPH oxidase, however, NETosis induced by Ca2+ ionophores was suggested to be mediated by ROS produced in mitochondria (mtROS).Using the mitochondria-targeted antioxidant SkQ1 and specific inhibitors of NADPH oxidase, we showed that both sources of ROS, mitochondria and NADPH oxidase, are involved in NETosis induced by A23187 in human neutrophils. In support of the critical role of mtROS, SkQ1-sensitive NETosis was demonstrate...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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In conclusion, taller body height at the entry to adulthood, supposed to be a marker of early-life environment, is associated with lower risk of dementia diagnosis later in life. The association persisted when adjusted for educational level and intelligence test scores in young adulthood, suggesting that height is not just acting as an indicator of cognitive reserve. A Comparison of Biological Age Measurement Approaches https://www.fightaging.org/archives/2020/02/a-comparison-of-biological-age-measurement-approaches/ Researchers here assess the performance of a range of approaches to measuring biological...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This is the latest in a series of yearly posts in which I suggest areas of development for biotech startups I'd like to see actively developed as a part of the longevity industry in the near future. Today, this year, is a good time to be starting a company focused on the production of a novel therapeutic approach to intervening in the aging process. There is a great deal of funding for seed stage investment, and many compelling projects lacking champions, yet to be carried forward from academia into preclinical development. Numerous scientific and industry crossover conferences are now held every year, at which it is possi...
Source: Fight Aging! - Category: Research Authors: Tags: Investment Source Type: blogs
In conclusion, the concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate. A Discussion of Recent Work on Allotopic Expression of Mitochondrial Genes at the SENS Research Foundation https://www.fightaging.org/archives/2020/02/a-discussion-of-recent-work-on-allotopic-expression-of-mitochondrial-genes-at-the-sens-research-foundation/ A paper published last month outlines recent progress on allotopic expression of mitochondrial genes carried out by the SENS Research ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusion: ROS promote CD8+ T cell activation by facilitating autoantigen cross-presentation by DCs. ROS scavengers could potentially represent an important component of therapies aiming to disrupt autoantigen presentation and activation of CD8+ T cells in individuals at-risk for developing T1D. In Type 1 Diabetes (T1D), pancreatic β cells are attacked by a T cell mediated autoimmune response and lose their ability to produce insulin (1–3). While a number of immune cell subsets are involved throughout the development of T1D, cytotoxic CD8+ T cells (CTLs) function as primary effectors of β cell damag...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Xuequn Xu†, J. N. Rashida Gnanaprakasam†, John Sherman† and Ruoning Wang* Center for Childhood Cancer and Blood Diseases, Hematology/Oncology &BMT, The Research Institute at Nationwide Children's Hospital, Ohio State University, Columbus, OH, United States The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) through genetic engineering is one of the most promising new therapies for treating cancer patients. A robust CAR T cell-mediated anti-tumor response requires the coordination of nutrient and energy supplies with CAR T cell expansion and function. Howe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Elvira Sondo1, Roberta Bertelli2, Emanuela Pesce1, Gian Marco Ghiggeri2 and Nicoletta Pedemonte1* 1UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, Genova, Italy 2UOC Nefrologia, IRCCS Istituto Giannina Gaslini, Genova, Italy Neutrophils migrate to sites of infection where they phagocytose, degranulate, and/or, in the presence of appropriate stimuli, release decondensed chromatin strands (called neutrophil extracellular traps, NETs) for trapping and possibly killing microorganisms. NET formation is characterized by marked morphological cell changes, in particular within the nucleus. Lytic NET formation can ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study found that professional chess players had shorter lifespans than those players who had careers outside of chess and argued that this might be due to the mental strain of international chess competition. In the present study, we focused on survival of International Chess Grandmasters (GMs) which represent players, of whom most are professional, at the highest level. In 2010, the overall life expectancy of GMs at the age of 30 years was 53.6 years, which is significantly greater than the overall weighted mean life expectancy of 45.9 years for the general population. In all three regions examined, mean life...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Discussion of advocacy for the cause is a usual feature of our community, as we try things and attempt to make progress in persuading the world that rejuvenation research is plausible, practical, and necessary. There are more people engaged in advocacy now than at any time in the past decade, and so discussions of strategy come up often. New ventures kicked off in 2017 include the Geroscience online magazine, and among the existing ventures the LEAF / Lifespan.io volunteers seem to be hitting their stride. The mainstream media continues to be as much a hindrance as a help, and where it is a help you will usually find Aubre...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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