Initiation of Neuronal Damage by Complex I Deficiency and Oxidative Stress in Parkinson's Disease

Tretter, László; Sipos, Ildikó; Ádám-Vizi, Vera

doi:10.1023/b:nere.0000014827.94562.4b

Cited by 182 publications

(118 citation statements)

References 102 publications

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“…This may potentially be due to the differences in the ROS produced by each stressor. Rotenone and tBHQ produce ROS indirectly by leakage of electrons from the electron transport chain and redox cycling, respectively [32]. H2O2 on the other hand, a ROS precursor, may directly interact with IRP, leading to its activation.…”

Section: Discussionmentioning

confidence: 99%

Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress

Mackenzie

Ray

Tsuji

2008

Free Radical Biology and Medicine

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Tight regulation of intracellular iron levels in response to mitochondrial dysfunction is an important mechanism that prevents oxidative stress, thereby limiting cellular damage. Here, we describe a cytoprotective response involving transcriptional activation of the ferritin H gene in response to the mitochondrial complex I inhibitor and neurotoxic compound, rotenone. Rotenone exposure increased ferritin H mRNA and protein synthesis in NIH3T3 fibroblasts and SH-SY5Y neuroblastoma cells. Transient transfection of a ferritin H promoter-luciferase reporter into NIH3T3 cells showed that ferritin H was transcriptionally activated by rotenone through an antioxidant responsive element (ARE). Chromatin immunoprecipitation assays showed that rotenone treatment enhanced binding of Nrf2 and JunD transcription factors to the ARE. In addition, rotenone induced production of reactive oxygen species (ROS), and pretreatment with N-acetylcysteine abrogated ferritin H mRNA induction by rotenone, suggesting that this response is oxidative stress-mediated. Furthermore, reduced ferritin H expression by siRNA sensitized cells to rotenone-induced apoptosis with enhanced ROS production and annexin V positive cells. Taken together, these results suggest that ferritin H transcription is activated by rotenone via an oxidative stress-mediated pathway leading to ARE activation, and may be critically important to protect cells from mitochondrial dysfunction and oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress

Mackenzie

Ray

Tsuji

2008

Free Radical Biology and Medicine

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“…The main sites of O 2 2 production in the ETC are complex I and III, with complex I being more predominant in skeletal muscle and neural cells; whereas complex III is more predominant for endothelial cells (Fig. 3) (323,416). O 2 2 generated by mitochondria reacts with manganese SOD (MnSOD) in the mitochondrial matrix to generate H 2 O 2 , which can cross the mitochondrial outer membrane to access cytosolic targets.…”

Section: B Mitochondrial-derived Ros In Inflammationmentioning

confidence: 99%

Reactive Oxygen Species in Inflammation and Tissue Injury

Mittal

Siddiqui

Tran

et al. 2014

Antioxidants & Redox Signaling

3,201

2,196

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Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury. Antioxid. Redox Signal. 20, 1126-1167.

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“…Since FR were accused as causal factors in a large number of diseases, these were sometimes referred as ''Free Radical Diseases''. Some of the important diseases and health issues in this category are cancer [61][62][63][64][65][66][67], cardiovascular diseases [68][69][70][71][72][73], atherosclerosis [74][75][76][77][78][79][80][81], neurological disorders [82][83][84][85][86], renal disorders [87][88][89][90], liver disorders [91][92][93], hypertension [50,94,95], rheumatoid arthritis [96,97], adult respiratory distress syndrome, auto-immune deficiency diseases [98,99], inflammation, degenerative disorders associated with aging [100][101][102][103], diabetes mellitus [104][105]…”

Section: Reactive Oxygen Species and Reactive Nitrogen Species Transimentioning

confidence: 99%

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

Singh

Chandra

Mahdi

et al. 2010

Indian J Clin Biochem

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The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2-2.8 lmol/l; 27.5-30 lmol/l; 40-50 lmol/l and 0.4-0.5 lmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overar...

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Initiation of Neuronal Damage by Complex I Deficiency and Oxidative Stress in Parkinson's Disease

Cited by 182 publications

References 102 publications

Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress

Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress

Reactive Oxygen Species in Inflammation and Tissue Injury

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

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