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Exercise Redox Signalling
Published in James N. Cobley, Gareth W. Davison, Oxidative Eustress in Exercise Physiology, 2022
Ruy A. Louzada, Jessica Bouviere, Rodrigo S. Fortunato, Denise P. Carvalho
The NADPH oxidase enzymes (NOXs) are unique proteins specialized in ROS production and are composed of seven members: NOX1 to NOX5 and DUOX1 and 2. Most of the NOXs have been reported to be present in skeletal muscle in vivo (Hori et al., 2011; Loureiro et al., 2016) (Figure 3.1). NOX2 is constitutively associated with the protein p22phox in the biological membrane. Activation of the NOX2-p22phox complex requires the translocation of cytosolic factors such as p47phox, p67phox, and p40phox to the membrane (Figure 3.1) (Henriquez-Olguin et al., 2020; Henríquez-Olguín et al., 2019a). NOX4 activity seems to be mainly dependent on its expression level, as well as the partial oxygen pressure (Ambasta et al., 2004; Ameziane-El-Hassani et al., 2016; Sun et al., 2011). Moreover, ATP can directly bind and negatively regulate NOX4 activity in the inner mitochondrial membrane, suggesting that subcellular redistribution of ATP levels from the mitochondria might act as an allosteric switch to activate NOX4 (Shanmugasundaram et al., 2017). While NOX2 and 4 produce , DUOX1/2 require maturation factors (DUOXA1/A2) to be targeted at the plasma membrane and generate H2O2 (Ameziane-El-Hassani et al., 2016; Carré et al., 2015; Louzada et al., 2018).
Anti-Inflammatory Properties of Bioactive Compounds from Medicinal Plants
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Health Benefits of Secondary Phytocompounds from Plant and Marine Sources, 2021
Muhammad Imran, Abdur Rauf, Anees Ahmed Khalil, Saud Bawazeer, Seema Patel, Zafar Ali Shah
In LPS-stimulated microglia, β-LAP (β-lapachone) from lapacho tree suppressed the iNOS expression, pro-inflammatory cytokines and MMPs (MMP-3, -8, and -9) at protein and mRNA levels. In contrast, β-LAP elevated the expressions of HO-1, IL-10, and TIMP-2 (tissue inhibitor of metalloproteinase-2). In an LPS-activated systemic inflammatory mouse model, anti-inflammatory potential associated with β-LAP was validated. In the LPS-treated mouse brain, β-LAP retarded activation of microglial and iNOS expressions, MMPs, and pro-inflammatory cytokines levels. Additionally, in LPS-activated microglia, studies regarding mode of action of β-LAP revealed anti-inflammatory potential by retarding NF-κB/AP-1, MAPKs, and PI3K/AKT signaling pathways. The β-LAP aided in suppressing the production of ROS by inhibiting phosphorylation of NADPH oxidase subunit proteins. Antioxidative properties of β-LAP seemed to increase NAD(P)H:quinone oxidoreductase-1 (NQO1) and HO-1 through Nrf2/ARE and PKA-pathways [74]. In mice (C57BL/6), β-LAP decreased, the instant hypersensitive response tempted by Con A (concanavalin A). Therefore, Th2 inhibited IL-10, IL-4, IL-6, and IL-5 averting the incidence of various allergic-inflammations and allergies [2].
Signalling Pathways in The Regulation of Cellular Responses to Exercise
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Anders Gudiksen, Stine Ringholm, Henriette Pilegaard
ROS signalling may be affected by ROS-induced ROS release, where mitochondrial-derived ROS affects NADPH oxidase or NADPH oxidase-derived ROS influences ROS production by the mitochondria (30). ROS signalling also interacts with the other well-characterized signalling pathways. Hence, ROS have been shown to alter Ca2+ release from the sarcoplasmic reticulum as well as the Ca2+ ATPase and hence Ca2+ reuptake in the sarcoplasmic reticulum (29, 106), suggesting a link between ROS and Ca2+ signalling. Furthermore, allopurinol treatment has been shown to prevent an exercise-induced increase in CREB phosphorylation (64) indicating an overlap between β-adrenergic signalling and ROS signalling. In addition, incubation in NAC reduced the contraction-induced increase in AMPK activity and phosphorylation together with preventing an increase in GSSG and GSSG/TGSH in isolated mouse SkM (104) providing evidence for an association between ROS and AMPK signalling. This is supported by observations in HEK cells and using recombinant AMPK that oxidation of AMPKα at cysteine residues 130 and 174 interfered with AMPK phosphorylation, while S-glutathionylation of Cys299 abd304 in AMPKα1/2 subunits increased the AMPK activity (138). Together these findings emphasize the complexity of exercise-induced ROS intracellular signalling.
The ubiquitous role of spleen tyrosine kinase (Syk) in gut diseases: From mucosal immunity to targeted therapy
Published in International Reviews of Immunology, 2022
Wenbin Gong, Peizhao Liu, Tao Zheng, Xiuwen Wu, Yun Zhao, Jianan Ren
Macrophages are widely recognized as essential players in the maintenance of intestinal homeostasis and as key guardians of the intestinal immune system [24]. It is reported that macrophage recognition of Salmonella enterica serovar Typhimurium triggers Syk phosphorylation and induces reactive oxygen species (ROS) production through a pathway that requires both triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX adaptor protein 12 (DAP12) [25]. ROS generation depends on the NADPH oxidase, and regulation of ROS production is a crucial innate immune defense against microbial pathogens [26]. Indeed, phosphorylation of Syk in response to a variety of stimuli can lead to activation of the NADPH oxidase and ROS production [27,28]. Syk phosphorylation activated by DAP12 also initiates an inflammatory signaling cascade in IBD and plays as an essential mediator in inflammation-driven immune dysfunction of experimental colitis [29]. Our recent studies have demonstrated that macrophage-inducible C-type lectin (Mincle) activates Syk by sensing spliceosome-associated protein 130 (SAP130) released from damaged intestinal epithelial cells during intestinal inflammation [30,31]. Increased Syk phosphorylation promotes the production of inflammatory cytokines through NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome mediated macrophage pyroptosis, which regulates intestinal mucosal immunity and promotes the disease progression of IBD [31].
Aortic dysfunction by chronic cadmium exposure is linked to multiple metabolic risk factors that converge in anion superoxide production
Published in Archives of Physiology and Biochemistry, 2022
Celeste Santamaria-Juarez, Fausto Atonal-Flores, Alfonso Diaz, Victor E. Sarmiento-Ortega, Miguel Garcia-Gonzalez, Patricia Aguilar-Alonso, Gustavo Lopez-Lopez, Eduardo Brambila, Samuel Treviño
In order to corroborate the participation of NADPH, in this work was used apocynin as a non-selective NADPH oxidase-inhibitor. Aortic rings of rats exposed to Cd and treated with apocynin showed the same relaxation pattern as aortic rings from rats without Cd-exposure (Emax and pD2; Figure 4(B)). This finding suggested that Cd is linked to an increase of NADPH oxidase activity, and that oxidative stress induced by this enzyme would reduce NO bioavailability (Berk 2007, Weseler and Bast 2010, Kukongviriyapan et al.2014). Apocynin inhibits NADPH oxidase (NOX) by binding to essential thiol groups of NADPH oxidase subunits, preventing the transfer of the soluble cytosolic subunits p47phox and p67phox to the cellular membrane, which is essential for •O2– production. Apocynin has been used in the administration of Cd acute or toxic, in the aorta (Beswick et al.2001, Nwokocha et al.2013, Rizzetti et al.2013, Oostwoud et al.2016). Similar treatment has been applied in vascular alterations induced by mercury, in which the co-treatment with apocynin restore the response to phenylephrine (Oostwoud et al.2016).
The relevant targets of anti-oxidative stress: a review
Published in Journal of Drug Targeting, 2021
The pathological mechanism of atherosclerotic (AS) involves several chronic vascular remodelling processes including oxidative stress. NADPH oxidase is the main source of ROS in atherosclerosis, which can induce the production of superoxide and aggravate oxidative stress, leading to the occurrence and development of arterial disease. Rutaecarpine can inhibit the activity of NADPH oxidase, down-regulate the expression of NADPH oxidase subunit Nox2, Nox4, and up-regulate the expression of regulatory protein p47phox, thus reducing the production of ROS and exerting anti-as effect [57–59]. In addition, inhibiting the activity of NADPH oxidase by preventing P47phox translocation to cell membrane is also an important mechanism of Parkinson’s therapy [60]. At present, novel targeted inhibitors of NADPH oxidase have been found, which can specifically target a variety of subtypes. NOX2ds-tat, the first polypeptide inhibitor targeting NADPH oxidase, inhibits the assembly of active NOX2 complexes by preventing the binding of NOX2B loop to its cytoplasmic domain p47phox, but polypeptide inhibitors are still in the stage of experimental research and have not been successfully used in clinic [61,62]. Also, it is found that targeted inhibitors of NADPH oxidase have a good effect on digestive system diseases and diabetes [63–65], but some inhibitors (e.g. Diphenyl iodine (DPI), Apocynin, 4-(2-Aminoethyl) benzenesulfonyl fluoride (AEBSF)) have disadvantages such as low efficiency, non-oral administration, off-target effect, which hinder their development into clinical drugs [66,67].