School Of Basic And Applied Sciences

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Subject: search.filters.subject.NADPH oxidase

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    Unveiling the mechanism of platelet dysfunction in Parkinson's disease: The effect of 6-hydroxydopamine on human blood platelets
    (Elsevier Ltd, 2023-05-22T00:00:00) Beura, Samir Kumar; Yadav, Pooja; Panigrahi, Abhishek Ramachandra; Singh, Sunil Kumar
    Introduction: Parkinson's disease (PD) is a progressive neuronal illness often linked to increased cardiovascular complications, such as myocardial infarction, cardiomyopathy, congestive heart failure, and coronary heart disease. Platelets, which are the essential components of circulating blood, are considered potential players in regulating these complications, as platelet dysfunction is evident in PD. These tiny blood cell fragments are supposed to play a crucial role in these complications, but the underlying molecular processes are still obscure. Methods: To gain a better understanding of platelet dysfunction in PD, we investigated the impact of 6-hydroxydopamine (6-OHDA), an analog of dopamine that simulates PD by destroying dopaminergic neurons, on human blood platelets. The levels of intraplatelet reactive oxygen species (ROS) were assessed using H2DCF-DA (20 ?M), while mitochondrial ROS was evaluated using MitoSOX� Red (5 ?M), and intracellular Ca2+ was measured with Fluo-4-AM (5 ?M). The data were acquired through the use of both a multimode plate reader and a laser-scanning confocal microscope. Results: Our findings showed that 6-OHDA treatment increased the production of ROS in human blood platelets. The increase in ROS was confirmed by the ROS scavenger, NAC, and was also reduced by inhibiting the NOX enzyme with apocynin. Additionally, 6-OHDA potentiated mitochondrial ROS production in platelets. Furthermore, 6-OHDA triggered the intraplatelet Ca2+ elevation. This effect was mitigated by the Ca2+ chelator BAPTA, which decreased the ROS production triggered by 6-OHDA in human blood platelets, while the IP3 receptor blocker, 2-APB, reduced the formation of ROS induced by 6-OHDA. Conclusion: Our findings suggest that the 6-OHDA-induced ROS production is regulated by the IP3 receptor-Ca2+-NOX signaling axis in human blood platelets, where the platelet mitochondria also play a significant role. This observation provides a crucial mechanistic understanding of the altered platelet activities that are commonly observed in PD patients. � 2023 Elsevier Ltd
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    MicroRNA Targeting Nicotinamide Adenine Dinucleotide Phosphate Oxidases in Cancer
    (Mary Ann Liebert Inc., 2020) Kushwaha P.P.; Gupta S.; Singh A.K.; Prajapati K.S.; Shuaib M.; Kumar S.
    Significance: Reactive oxygen species (ROS) production occurs primarily in the mitochondria as a by-product of cellular metabolism. ROS are also produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases in response to growth factors and cytokines by normal physiological signaling pathways. NADPH oxidase, a member of NADPH oxidase (NOX) family, utilizes molecular oxygen (O2) to generate ROS such as hydrogen peroxide and superoxide. Imbalance between ROS production and its elimination is known to be the major cause of various human diseases. NOX family proteins are exclusively involved in ROS production, which makes them attractive target(s) for the treatment of ROS-mediated diseases including cancer. Recent Advances: Molecules such as Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2), N-methyl-d-aspartic acid (NMDA) receptors, nuclear factor-kappaB, KRAS, kallistatin, gene associated with retinoic-interferon-induced mortality-19, and deregulated metabolic pathways are involved in ROS production in association with NADPH oxidase. Critical Issues: Therapeutic strategies targeting NADPH oxidases in ROS-driven cancers are not very effective due to its complex regulatory circuit. Tumor suppressor microRNAs (miRNAs) viz. miR-34a, miR-137, miR-99a, and miR-21a-3p targeting NADPH oxidases are predominantly downregulated in ROS-driven cancers. miRNAs also regulate other cellular machineries such as Keap1/Nrf2 pathway and NMDA receptors involved in ROS production and consequently drug resistance. Here, we discuss the structure, function, and metabolic role of NADPH oxidase, NOX family protein-protein interaction, their association with other pathways, and NADPH oxidase alteration by miRNAs. Moreover, we also discuss and summarize studies on NADPH oxidase associated with various malignancies and their therapeutic implications. Future Directions: Targeting NADPH oxidases through miRNAs appears to be a promising strategy for the treatment of ROS-driven cancer.
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    Pollen induced stress in human lung carcinoma A549 cells
    (Central University of Punjab, 2014) Atri, Rekha; Dhiman, Monisha
    The pollen grains are important aeroallergens causing allergic disorders like rhinitis and asthma. Chronic asthma often leads to carcinogenesis in lungs. The various mediators of inflammation like reactive oxygen and nitrogen species (ROS/RNS), cytokines and chemokines form a link between oxidative stress, inflammation and cancer. This study involves induction of oxidative stress by pollen extracts derived from two varieties of prickly poppy in small lung carcinoma A549 cells. To rule out the pathway responsible for pro-inflammatory and oxidative stress enhancer we used the inhibitors of the classical ROS sources such as NADPH oxidase, Xanthine oxidase, mitochondria and general ROS scavenger (NAC). In addition, we also used NF-kB blocking peptide to see whether blocking NF-kB pathway can attenuate the pollen induced stress. It was observed that there was no significant difference in inflammation and/or oxidative stress in the purified pollen antigen versus the crude pollen extract. Lipid peroxidation was significantly increased in pollen extract treated cells whereas no change in MPO activity was observed. The NF-kB levels were significantly reduced in pollen extract treated cells whereas the levels were normalised when treated with NOX inhibitor (DPI) and mitochondria uncoupler (FCCP) suggesting the role of mitochondrial and phagocytic ROS in activating NF-kB. This study signifies the role of pollen as aero-allergens which are very common in Malwa region of Punjab as a key player in enhancing the allergy related complications and chronic lung diseases.