Biological and physiological role of reactive oxygen species - the good, the bad and the ugly

Zuo, Li; Zhou, Tingyang; Pannell, Benjamin K.; Ziegler, A; Best, Thomas M.

doi:10.1111/apha.12515

Cited by 340 publications

(264 citation statements)

References 232 publications

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“…3) ROS can be direct cytotoxicity or may pose potential risk of cell death by transforming into free radicals that react with macromolecules, DNA, proteins and lipids. 22) t-BHP may stimulate ROS generation and therefore was used to induce conditions of oxidative stress. Previous studies found that mitochondria, a source of ROS and a sensor of oxidative stress, play a key role in the transduction and amplification of the apoptotic response in cardiomyocytes during oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway

Zhang¹,

Hu²,

Luo³

et al. 2017

Biological & Pharmaceutical Bulletin

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In this study, we investigated the cardioprotective mechanisms of action of DT-010, a novel danshensutetramethylpyrazine conjugate. DT-010 significantly preserved cell viability and suppressed cell apoptosis in H9c2 cells injured by tert-butylhydroperoxide (t-BHP), iodoacetic acid (IAA) and hypoxia-reoxygenation. In addition, DT-010 pre-treatment reduced the intracellular level of free radicals including superoxide anion (·O 2 ), hydroxyl radical (·OH) and peroxynitrite anion (ONOO ) after t-BHP exposure. Moreover, DT-010 up-regulated the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) as well as mitochondrial transcription factor A (Tfam) and heme oxygenase-1 (HO-1) in H9c2 cells. DT-010 also triggered Nrf2 nuclear translocation. In a rat myocardial ischemia-reperfusion model, DT-010 significantly alleviated myocardial infarction. The results indicated that DT-010 may be a promising candidate for the treatment of cardiovascular diseases, particularly myocardial ischemia and reperfusion injury.Key words Danshensu derivative; oxidative stress; apoptosis; myocardial ischemia reperfusion injury; peroxisome proliferator-activated receptor gamma coactivator 1 alpha/nuclear factor-E2-related factor 2/heme oxygenase-1 (PGC-1α/Nrf2/HO-1) pathway Myocardial ischemia is a primary cause of sudden death worldwide. Myocardial ischemia results from a decreased blood flow to the heart, preventing the heart from receiving adequate supply of energy. The reduced blood flow is usually caused by a partial or complete blockade of the arteries. Traditional treatments focus on restoring blood supply, such as by pass-graft surgery, dilation of coronary artery and coronary thrombolysis, and etc. 1) Although restoration of blood flow to the ischemic heart tissues is important, it is not adequate because myocardial ischemic damage is progressively developed following reperfusion due to an over-production of a large number of biospecies. 2,3) Compelling evidence demonstrated that free radicals generated during ischemia and reperfusion play pivotal roles in myocardial apoptosis. Free radical scavengers can effectively inhibit myocardial apoptosis. The previous studies have demonstrated that agents that combine anti-thrombolytic and anti-oxidative activities showed promising therapeutic efficacy in the treatment of myocardial ischemia. 4,5) In China, many traditional herbs have been used to prevent and treat myocardial ischemia. Among them are Salvia miltiorrhiza (Danshen) and Ligusticum wallichii (Chuanxiong). As the major active ingredients, (3-(3,4-dihydroxyphenyl) lactic acid) (Danshensu, DSS, Fig. 1) isolated from Danshen and tetramethylpyrazine (TMP, Fig. 1) isolated from Chuanxiong have a variety of biological activities. They lyse blood clot, dilate coronary arteries, inhibit platelet aggregation, scavenge free radicals, improve microcirculation and have anti-inflammatory properties. 6,7) Both of them are widely used in clinic for treatm...

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Section: Discussionmentioning

confidence: 99%

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway

Zhang¹,

Hu²,

Luo³

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Endogenous ROS/RNS production arises from the mitochondrial-resident electron transport chain (ETC), from the action of different enzymes [i.e., NAD(P)H oxidases (NOXs), xanthine oxidase (XO), nitric oxide synthase (NOS), lipoxygenase, cyclooxygenase, cytochrome P450s] as well as from redox metal ion-catalyzed reactions involving iron or copper (i.e., Fenton reaction). ROS/ RNS can have both positive and potentially damaging effects, depending on their nature, concentration and duration [2,3,22,23]. At low/moderate levels, ROS/RNS possess highly specialized physiological functions with positive actions in redox-sensitive signaling that coordinate basic activities of cells.…”

Section: Nrf2 As Regulator Of Redox Homeostasismentioning

confidence: 99%

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Paladino

Conte

Caggiano

et al. 2018

Cell Physiol Biochem

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A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2.

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“…These two paradoxical functions of ROS, depended on how well our body can regulate and control their production, can be viewed as the Janus faces (Figure 7). ROS under normal circumstance exert critical actions in cells such as signal transduction, gene transcription and immune response [91]. Superoxide anion produced by NADPH oxidase is vitally important in killing invaded pathogens in phagocytic cells (macrophages, monocytes, neutrophils, eosinophils) through respiratory burst or oxidative burst (Figure 8).…”

Section: Roles Of Ros In Physiology and Pathologymentioning

confidence: 99%

Oxidative Stress in Urolithiasis

Boonla¹

2018

Reactive Oxygen Species (ROS) in Living Cells

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Oxygen is absolutely essential for the survival of our life. However, metabolic consumption of oxygen inevitably yields reactive oxygen species (ROS). Imbalance of ROS production and antioxidant capacity causes oxidative stress that potentially damages biomolecules leading to cell injury and death. In fact, ROS have two-faceted functions. Under physiologic condition, ROS function as signaling molecules and participate in maintaining redox balance. In pathology, ROS induce oxidative stress that critically involves in the development of several diseases including urolithiasis (UL). UL or urinary stone disease is a common urologic condition in all countries with progressively increasing prevalence. Most of UL are multifactorial with polygenic susceptibility and highly recurrent nature. Formation of urinary stones is driven by supersaturation of urinary lithogenic ions, and calcium oxalate (CaOx) is the most prevalent stone type. Oxidative stress clearly plays an active role in UL development. In vitro, lithogenic crystals induce ROS generation in renal tubular cells leading to oxidative stress, cell injury and release of inflammatory mediators. In nephrolithic rats, oxidative stress and CaOx deposit are gradually increased in the rats' kidneys. Intervention with antioxidants efficiently reduces oxidative damage and crystal deposits. Human studies show that patients with UL have increased oxidative stress and renal tubular injury relative to the non-stone-forming individuals. Increased oxidative lesions and inflammation are observed in the stone-containing kidneys of the patients. Furthermore, renal fibrosis mediated through tubular epithelial-mesenchymal transition is observed in kidneys of stone patients. Increased renal fibrosis is significantly associated with decreased kidney function. From therapeutic point of view, nutraceutical regimens that are able to reduce oxidative stress may be clinically useful alternatives for preventing stone formation and recurrence. This chapter has an intention to provide a basic knowledge of ROS generation and oxidative stress and up-to-date research findings of oxidative stress in UL based on the published articles as well as the author's studies.

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Biological and physiological role of reactive oxygen species - the good, the bad and the ugly

Cited by 340 publications

References 232 publications

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Oxidative Stress in Urolithiasis

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