Browsing by Subject "ROS"
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Item 17Beta-Estradiol Suppresses Hydrogen Peroxide-Induced Nuclear Factor Kappa B Activation in HT22 Cells(2008-05-01) Kim, Pil J.; Simpkins; Singh; Yang, ShaohuaKim, Pil J., 17beta-estradiol suppresses hydrogen peroxide-induced nuclear factor κappa B activation in HT22 cells. Master of Science (Biomedical Sciences), May, 2008, 78pp., 20 illustrations, 66 titles. Reactive oxygen species (ROS) are natural byproducts of normal cellular reactions. They are oxygen ions, free (non)radicals, and peroxides that are highly reactive with normal macromolecules, such as lipids, DNA, and proteins. Cells are normally able to defend against the damages of ROS via enzymes that neutralize them into water. However, when cells are not able to cope with the accumulation of ROS, distributions in signaling pathways and gene transcription will occur, which will ultimately lead to cell death. It is now widely accepted that increased oxidative stress-induced damage in the brain is a major cause of neurodegenerative diseases, such as Alzheimer’s disease (AD). Nuclear factor κappa-B (NFκB) is not only a ubiquitously expressed transcription factor but also a signaling protein that is activated by ROS-induced oxidative stress. Our laboratory has demonstrated the neuroprotective effects of 17β-estradiol (E2) are elicited via an anti-oxidant effect. The purpose of this project was to determine the role of NFκB activation in E2-mediated neuroprotection against hydrogen peroxide (H2O2)-induced oxidative stress. HT-22, a murine immortalized hippocampal neuronal cell line, was utilized to determine whether NFκB is activated by hydrogen peroxide-induced oxidative stress and whether E2 suppresses H2O2-induced NFκB activation. We observed that H2O2 activated NFκB by phosphorylation of IκBα (pIκBα), one of the NFκB inhibitor proteins, reduction of total IκBα, and induction of NFκB (p65) nuclear translocation. In contrast, E2 suppressed H2O2-induced NFκB activation by dramatic reducing pIκBα, increasing total IκBα, and inhibiting p65 nuclear translocation. Our results show that one of the mechanisms by which estrogens are neuroprotective against oxidative stress is through the attenuation of H2O2-induced NFκB activation.Item Modulating mitochondrial calcium channels (TRPM2/MCU/NCX) as a therapeutic strategy for neurodegenerative disorders(Frontiers Media S.A., 2023-11-06) Johnson, Gretchen A.; Krishnamoorthy, Raghu R.; Stankowska, Dorota L.Efficient cellular communication is essential for the brain to regulate diverse functions like muscle contractions, memory formation and recall, decision-making, and task execution. This communication is facilitated by rapid signaling through electrical and chemical messengers, including voltage-gated ion channels and neurotransmitters. These messengers elicit broad responses by propagating action potentials and mediating synaptic transmission. Calcium influx and efflux are essential for releasing neurotransmitters and regulating synaptic transmission. Mitochondria, which are involved in oxidative phosphorylation, and the energy generation process, also interact with the endoplasmic reticulum to store and regulate cytoplasmic calcium levels. The number, morphology, and distribution of mitochondria in different cell types vary based on energy demands. Mitochondrial damage can cause excess reactive oxygen species (ROS) generation. Mitophagy is a selective process that targets and degrades damaged mitochondria via autophagosome-lysosome fusion. Defects in mitophagy can lead to a buildup of ROS and cell death. Numerous studies have attempted to characterize the relationship between mitochondrial dysfunction and calcium dysregulation in neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic lateral sclerosis, spinocerebellar ataxia, and aging. Interventional strategies to reduce mitochondrial damage and accumulation could serve as a therapeutic target, but further research is needed to unravel this potential. This review offers an overview of calcium signaling related to mitochondria in various neuronal cells. It critically examines recent findings, exploring the potential roles that mitochondrial dysfunction might play in multiple neurodegenerative diseases and aging. Furthermore, the review identifies existing gaps in knowledge to guide the direction of future research.