Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum

Konno, Tasuku; Melo, Eduardo P.; Chambers, Joseph E.; Avezov, Edward

doi:10.3390/cells10020233

Cited by 82 publications

(50 citation statements)

References 253 publications

(260 reference statements)

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“…In the cell, there are other sources of ROS, such as the endoplasmic reticulum (ER), nucleus, peroxisomes, and even the Golgi apparatus. The production of ROS through the NADPH oxidases (NOX) family, considered a major source of ROS in eukaryotic cells, in the membranes of these compartments, and the cytoplasmatic membranes of the cells are higher than in the mitochondria [ 24 , 25 ]. NOX family constitutes the only professional primary oxidases since other enzymes such as, for example, xanthine oxidase (XO) or monoamine oxidases (MAO) produce ROS as a consequence of their primary metabolic function [ 26 ].…”

Section: Mitros the First In The Aging Processmentioning

confidence: 99%

The Role of Immune Cells in Oxi-Inflamm-Aging

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et al. 2021

Cells

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Aging is the result of the deterioration of the homeostatic systems (nervous, endocrine, and immune systems), which preserve the organism’s health. We propose that the age-related impairment of these systems is due to the establishment of a chronic oxidative stress situation that leads to low-grade chronic inflammation throughout the immune system’s activity. It is known that the immune system weakens with age, which increases morbidity and mortality. In this context, we describe how the function of immune cells can be used as an indicator of the rate of aging of an individual. In addition to this passive role as a marker, we describe how the immune system can work as a driver of aging by amplifying the oxidative-inflammatory stress associated with aging (oxi-inflamm-aging) and inducing senescence in far tissue cells. Further supporting our theory, we discuss how certain lifestyle conditions (such as social environment, nutrition, or exercise) can have an impact on longevity by affecting the oxidative and inflammatory state of immune cells, regulating immunosenescence and its contribution to oxi-inflamm-aging.

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Section: Mitros the First In The Aging Processmentioning

confidence: 99%

The Role of Immune Cells in Oxi-Inflamm-Aging

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Ceprián

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et al. 2021

Cells

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“…With its ability to shift between two redox states, non-bound iron is highly reactive, leading to oxidative stress which is a pivotal trigger of tissue and organ failure [ 15 ]. The key step for the excessive production of radicals is the Fenton reaction, which has been demonstrated to play a fundamental role in the physiopathology of several diseases, including heart failure [ 45 ], liver failure [ 46 ], renal disease [ 47 ], and different types of neurodegeneration [ 48 , 49 , 50 ]. Cardiomyopathies related to iron-overload represent one of the major causes of mortality and comorbidity in patients with secondary and primary hemochromatosis, respectively [ 15 , 51 , 52 , 53 ].…”

Section: Iron and Oxidative Stress In Cardiomyocytes And Hepatocytesmentioning

confidence: 99%

Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

et al. 2021

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Iron accumulation is a key mediator of several cytotoxic mechanisms leading to the impairment of redox homeostasis and cellular death. Iron overload is often associated with haematological diseases which require regular blood transfusion/phlebotomy, and it represents a common complication in thalassaemic patients. Major damages predominantly occur in the liver and the heart, leading to a specific form of cell death recently named ferroptosis. Different from apoptosis, necrosis, and autophagy, ferroptosis is strictly dependent on iron and reactive oxygen species, with a dysregulation of mitochondrial structure/function. Susceptibility to ferroptosis is dependent on intracellular antioxidant capacity and varies according to the different cell types. Chemotherapy-induced cardiotoxicity has been proven to be mediated predominantly by iron accumulation and ferroptosis, whereas there is evidence about the role of ferritin in protecting cardiomyocytes from ferroptosis and consequent heart failure. Another paradigmatic organ for transfusion-associated complication due to iron overload is the liver, in which the role of ferroptosis is yet to be elucidated. Some studies report a role of ferroptosis in the initiation of hepatic inflammation processes while others provide evidence about an involvement in several pathologies including immune-related hepatitis and acute liver failure. In this manuscript, we aim to review the literature to address putative common features between the response to ferroptosis in the heart and liver. A better comprehension of (dys)similarities is pivotal for the development of future therapeutic strategies that can be designed to specifically target this type of cell death in an attempt to minimize iron-overload effects in specific organs.

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“…Peroxisomes contain several oxidative enzymes that result in hydrogen peroxide production, as well as catalase, an enzyme that, under non-pathological conditions, is able to decompose hydrogen peroxide into water and oxygen [ 8 ]. The endoplasmic reticulum is another source of ROS, derived from reactions required for protein folding or from NADPH oxidase (NOX) isoforms found in the endoplasmic reticulum [ 9 ]. Other sources of ROS are lysosomes, nuclei, cell membrane and the cytoplasm via NOX, nitric oxide synthases, or as a consequence spontaneous autoxidation [ 10 , 11 ].…”

Section: Oxidative Stress In the Central Nervous Systemmentioning

confidence: 99%

NRF2 Activation and Downstream Effects: Focus on Parkinson’s Disease and Brain Angiotensin

et al. 2021

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Reactive oxygen species (ROS) are signalling molecules used to regulate cellular metabolism and homeostasis. However, excessive ROS production causes oxidative stress, one of the main mechanisms associated with the origin and progression of neurodegenerative disorders such as Parkinson’s disease. NRF2 (Nuclear Factor-Erythroid 2 Like 2) is a transcription factor that orchestrates the cellular response to oxidative stress. The regulation of NRF2 signalling has been shown to be a promising strategy to modulate the progression of the neurodegeneration associated to Parkinson’s disease. The NRF2 pathway has been shown to be affected in patients with this disease, and activation of NRF2 has neuroprotective effects in preclinical models, demonstrating the therapeutic potential of this pathway. In this review, we highlight recent advances regarding the regulation of NRF2, including the effect of Angiotensin II as an endogenous signalling molecule able to regulate ROS production and oxidative stress in dopaminergic neurons. The genes regulated and the downstream effects of activation, with special focus on Kruppel Like Factor 9 (KLF9) transcription factor, provide clues about the mechanisms involved in the neurodegenerative process as well as future therapeutic approaches.

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Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum

Cited by 82 publications

References 253 publications

The Role of Immune Cells in Oxi-Inflamm-Aging

The Role of Immune Cells in Oxi-Inflamm-Aging

Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

NRF2 Activation and Downstream Effects: Focus on Parkinson’s Disease and Brain Angiotensin

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