Reactive Oxygen Species (Ros-Induced) Ros Release

We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes via photoactivation of tetramethylrhodamine derivatives, which also served to report the mitochondrial transmembrane potential, ΔΨ. This ROS accumulation reproducibly triggered abrupt (and sometimes reversible) mitochondrial depolarization. This phenomenon was ascribed to MPT induction because (a) bongkrekic acid prevented it and (b) mitochondria became permeable for calcein (∼620 daltons) concurrently with depolarization. These photodynamically produced “triggering” ROS caused the MPT induction, as the ROS scavenger Trolox prevented it. The time required for triggering ROS to induce the MPT was dependent on intrinsic cellular ROS-scavenging redox mechanisms, particularly glutathione. MPT induction caused by triggering ROS coincided with a burst of mitochondrial ROS generation, as measured by dichlorofluorescein fluorescence, which we have termed mitochondrial “ROS-induced ROS release” (RIRR). This MPT induction/RIRR phenomenon in cardiac myocytes often occurred synchronously and reversibly among long chains of adjacent mitochondria demonstrating apparent cooperativity. The observed link between MPT and RIRR could be a fundamental phenomenon in mitochondrial and cell biology.

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Cross talk between increased intracellular zinc (Zn2+) and accumulation of reactive oxygen species in chemical ischemia

AJP Cell Physiology ◽

10.1152/ajpcell.00048.2017 ◽

2017 ◽

Vol 313 (4) ◽

pp. C448-C459 ◽

Cited By ~ 19

Author(s):

Kira G. Slepchenko ◽

Qiping Lu ◽

Yang V. Li

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Cross Talk ◽

Reactive Oxygen ◽

Glucose Deprivation ◽

Ros Generation ◽

Oxygen Species ◽

Mitochondrial Ros ◽

Ros Accumulation ◽

Ischemic Stress

Both zinc (Zn2+) and reactive oxygen species (ROS) have been shown to accumulate during hypoxic-ischemic stress and play important roles in pathological processes. To understand the cross talk between the two of them, here we studied Zn2+ and ROS accumulation by employing fluorescent probes in HeLa cells to further the understanding of the cause and effect relationship of these two important cellular signaling systems during chemical-ischemia, stimulated by oxygen and glucose deprivation (OGD). We observed two Zn2+ rises that were divided into four phases in the course of 30 min of OGD. The first Zn2+ rise was a transient, which was followed by a latent phase during which Zn2+ levels recovered; however, levels remained above a basal level in most cells. The final phase was the second Zn2+ rise, which reached a sustained plateau called Zn2+ overload. Zn2+ rises were not observed when Zn2+ was removed by TPEN (a Zn2+ chelator) or thapsigargin (depleting Zn2+ from intracellular stores) treatment, indicating that Zn2+ was from intracellular storage. Damaging mitochondria with FCCP significantly reduced the second Zn2+ rise, indicating that the mitochondrial Zn2+ accumulation contributes to Zn2+ overload. We also detected two OGD-induced ROS rises. Two Zn2+ rises preceded two ROS rises. Removal of Zn2+ reduced or delayed OGD- and FCCP-induced ROS generation, indicating that Zn2+ contributes to mitochondrial ROS generation. There was a Zn2+-induced increase in the functional component of NADPH oxidase, p47phox, thus suggesting that NADPH oxidase may mediate Zn2+-induced ROS accumulation. We suggest a new mechanism of cross talk between Zn2+ and mitochondrial ROS through positive feedback processes that eventually causes excessive free Zn2+ and ROS accumulations during the course of ischemic stress.

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Ginger Oleoresin Alleviated γ-Ray Irradiation-Induced Reactive Oxygen Species via the Nrf2 Protective Response in Human Mesenchymal Stem Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/1480294 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Kaihua Ji ◽

Lianying Fang ◽

Hui Zhao ◽

Qing Li ◽

Yang Shi ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Mesenchymal Stem Cells ◽

Reactive Oxygen ◽

Ros Generation ◽

Oxygen Species ◽

Ros Scavenging ◽

Genes Encoding ◽

Dna Strand

Unplanned exposure to radiation can cause side effects on high-risk individuals; meanwhile, radiotherapies can also cause injury on normal cells and tissues surrounding the tumor. Besides the direct radiation damage, most of the ionizing radiation- (IR-) induced injuries were caused by generation of reactive oxygen species (ROS). Human mesenchymal stem cells (hMSCs), which possess self-renew and multilineage differentiation capabilities, are a critical population of cells to participate in the regeneration of IR-damaged tissues. Therefore, it is imperative to search effective radioprotectors for hMSCs. This study was to demonstrate whether natural source ginger oleoresin would mitigate IR-induced injuries in human mesenchymal stem cells (hMSCs). We demonstrated that ginger oleoresin could significantly reduce IR-induced cytotoxicity, ROS generation, and DNA strand breaks. In addition, the ROS-scavenging mechanism of ginger oleoresin was also investigated. The results showed that ginger oleoresin could induce the translocation of Nrf2 to cell nucleus and activate the expression of cytoprotective genes encoding for HO-1 and NQO-1. It suggests that ginger oleoresin has a potential role of being an effective antioxidant and radioprotective agent.

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On the Origin and Fate of Reactive Oxygen Species in Plant Cell Compartments

Antioxidants ◽

10.3390/antiox8040105 ◽

2019 ◽

Vol 8 (4) ◽

pp. 105 ◽

Cited By ~ 32

Author(s):

Janků ◽

Luhová ◽

Petřivalský

Keyword(s):

Reactive Oxygen Species ◽

Plant Cell ◽

Nitrosative Stress ◽

Reactive Oxygen ◽

Redox Status ◽

Stress Conditions ◽

Ros Generation ◽

Oxygen Species ◽

Ros Scavenging ◽

Cell Compartments

Reactive oxygen species (ROS) have been recognized as important signaling compoundsof major importance in a number of developmental and physiological processes in plants. Theexistence of cellular compartments enables efficient redox compartmentalization and ensuresproper functioning of ROS‐dependent signaling pathways. Similar to other organisms, theproduction of individual ROS in plant cells is highly localized and regulated bycompartment‐specific enzyme pathways on transcriptional and post‐translational level. ROSmetabolism and signaling in specific compartments are greatly affected by their chemicalinteractions with other reactive radical species, ROS scavengers and antioxidant enzymes. Adysregulation of the redox status, as a consequence of induced ROS generation or decreasedcapacity of their removal, occurs in plants exposed to diverse stress conditions. During stresscondition, strong induction of ROS‐generating systems or attenuated ROS scavenging can lead tooxidative or nitrosative stress conditions, associated with potential damaging modifications of cellbiomolecules. Here, we present an overview of compartment‐specific pathways of ROS productionand degradation and mechanisms of ROS homeostasis control within plant cell compartments.

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Mitochondrial Reactive Oxygen Species Mediate GPCR–induced TACE/ADAM17-dependent Transforming Growth Factor-α Shedding

Molecular Biology of the Cell ◽

10.1091/mbc.e08-12-1256 ◽

2009 ◽

Vol 20 (24) ◽

pp. 5236-5249 ◽

Cited By ~ 48

Author(s):

Timothy J. Myers ◽

Leann H. Brennaman ◽

Mary Stevenson ◽

Shigeki Higashiyama ◽

William E. Russell ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Growth Factor ◽

Transforming Growth Factor ◽

Reactive Oxygen ◽

Oxygen Species ◽

Ros Scavenging ◽

Transforming Growth Factor Α ◽

Egfr Activation ◽

Mitochondrial Ros ◽

Factor Α

Epidermal growth factor receptor (EGFR) activation by GPCRs regulates many important biological processes. ADAM metalloprotease activity has been implicated as a key step in transactivation, yet the regulatory mechanisms are not fully understood. Here, we investigate the regulation of transforming growth factor-α (TGF-α) shedding by reactive oxygen species (ROS) through the ATP-dependent activation of the P2Y family of GPCRs. We report that ATP stimulates TGF-α proteolysis with concomitant EGFR activation and that this process requires TACE/ADAM17 activity in both murine fibroblasts and CHO cells. ATP-induced TGF-α shedding required calcium and was independent of Src family kinases and PKC and MAPK signaling. Moreover, ATP-induced TGF-α shedding was completely inhibited by scavengers of ROS, whereas calcium-stimulated shedding was partially inhibited by ROS scavenging. Hydrogen peroxide restored TGF-α shedding after calcium chelation. Importantly, we also found that ATP-induced shedding was independent of the cytoplasmic NADPH oxidase complex. Instead, mitochondrial ROS production increased in response to ATP and mitochondrial oxidative complex activity was required to activate TACE-dependent shedding. These results reveal an essential role for mitochondrial ROS in regulating GPCR-induced growth factor shedding.

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Role of Reactive Oxygen Species in Pathogenesis of Radiocontrast-Induced Nephropathy

BioMed Research International ◽

10.1155/2013/868321 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 39

Author(s):

Antonio Pisani ◽

Eleonora Riccio ◽

Michele Andreucci ◽

Teresa Faga ◽

Michael Ashour ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Contrast Media ◽

Reactive Oxygen ◽

In Vivo Studies ◽

Ros Generation ◽

Oxygen Species ◽

Ros Scavenging ◽

Iodinated Contrast ◽

Ros Formation

In vitro and in vivo studies have demonstrated enhanced hypoxia and formation of reactive oxygen species (ROS) in the kidney following the administration of iodinated contrast media, which play a relevant role in the development of contrast media-induced nephropathy. Many studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetylcysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy, are prone to enhanced renal parenchymal hypoxia and ROS formation. In this review, the association of renal hypoxia and ROS-mediated injury is outlined. Generated during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular and vascular endothelial injury and might further intensify renal parenchymal hypoxia by virtue of endothelial dysfunction and dysregulation of tubular transport. Preventive strategies conceivably should include inhibition of ROS generation or ROS scavenging.

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Reactive Oxygen Species: A Promising Therapeutic Target for SDHx-Mutated Pheochromocytoma and Paraganglioma

Cancers ◽

10.3390/cancers13153769 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3769

Author(s):

Katerina Hadrava Hadrava Vanova ◽

Chunzhang Yang ◽

Leah Meuter ◽

Jiri Neuzil ◽

Karel Pacak

Keyword(s):

Reactive Oxygen Species ◽

Tumor Cells ◽

Reactive Oxygen ◽

Ros Production ◽

Oxygen Species ◽

Ros Scavenging ◽

Promising Therapeutic Target ◽

Ros Accumulation ◽

Intracellular Ros

Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors derived from neural crest cells. Germline variants in approximately 20 PHEO/PGL susceptibility genes are found in about 40% of patients, half of which are found in the genes that encode succinate dehydrogenase (SDH). Patients with SDH subunit B (SDHB)-mutated PHEO/PGL exhibit a higher likelihood of developing metastatic disease, which can be partially explained by the metabolic cell reprogramming and redox imbalance caused by the mutation. Reactive oxygen species (ROS) are highly reactive molecules involved in a multitude of important signaling pathways. A moderate level of ROS production can help regulate cellular physiology; however, an excessive level of oxidative stress can lead to tumorigenic processes including stimulation of growth factor-dependent pathways and the induction of genetic instability. Tumor cells effectively exploit antioxidant enzymes in order to protect themselves against harmful intracellular ROS accumulation, which highlights the essential balance between ROS production and scavenging. Exploiting ROS accumulation can be used as a possible therapeutic strategy in ROS-scavenging tumor cells. Here, we focus on the role of ROS production in PHEO and PGL, predominantly in SDHB-mutated cases. We discuss potential strategies and approaches to anticancer therapies by enhancing ROS production in these difficult-to-treat tumors.

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Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1616781 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 34

Author(s):

Lun Zhang ◽

Jiahui Li ◽

Liang Zong ◽

Xin Chen ◽

Ke Chen ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Pancreatic Cancer ◽

Cancer Cells ◽

Biological Activities ◽

Reactive Oxygen ◽

The United States ◽

Ros Generation ◽

Oxygen Species ◽

Ros Scavenging ◽

Pancreatic Cancer Cells

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy.

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Every Coin Has Two Sides: Reactive Oxygen Species during Rice–Magnaporthe oryzae Interaction

International Journal of Molecular Sciences ◽

10.3390/ijms20051191 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1191 ◽

Cited By ~ 4

Author(s):

Yanjun Kou ◽

Jiehua Qiu ◽

Zeng Tao

Keyword(s):

Reactive Oxygen Species ◽

Magnaporthe Oryzae ◽

Rice Blast ◽

Blast Resistance ◽

Reactive Oxygen ◽

Redox Balance ◽

Ros Generation ◽

Oxygen Species ◽

Rice Blast Resistance ◽

Ros Accumulation

Reactive oxygen species (ROS) are involved in many important processes, including the growth, development, and responses to the environments, in rice (Oryza sativa) and Magnaporthe oryzae. Although ROS are known to be critical components in rice–M. oryzae interactions, their regulations and pathways have not yet been completely revealed. Recent studies have provided fascinating insights into the intricate physiological redox balance in rice–M. oryzae interactions. In M. oryzae, ROS accumulation is required for the appressorium formation and penetration. However, once inside the rice cells, M. oryzae must scavenge the host-derived ROS to spread invasive hyphae. On the other side, ROS play key roles in rice against M. oryzae. It has been known that, upon perception of M. oryzae, rice plants modulate their activities of ROS generating and scavenging enzymes, mainly on NADPH oxidase OsRbohB, by different signaling pathways to accumulate ROS against rice blast. By contrast, the M. oryzae virulent strains are capable of suppressing ROS accumulation and attenuating rice blast resistance by the secretion of effectors, such as AvrPii and AvrPiz-t. These results suggest that ROS generation and scavenging of ROS are tightly controlled by different pathways in both M. oryzae and rice during rice blast. In this review, the most recent advances in the understanding of the regulatory mechanisms of ROS accumulation and signaling during rice–M. oryzae interaction are summarized.

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Reactive oxygen species and seed germination

Biologia ◽

10.2478/s11756-013-0161-y ◽

2013 ◽

Vol 68 (3) ◽

Cited By ~ 58

Author(s):

Marcelo Gomes ◽

Queila Garcia

Keyword(s):

Reactive Oxygen Species ◽

Seed Germination ◽

Reactive Oxygen ◽

Environmental Cues ◽

Oxygen Species ◽

Ros Scavenging ◽

Endosperm Weakening ◽

Ros Accumulation ◽

Germination Success ◽

Seed Reserves

AbstractReactive oxygen species (ROS) are continuously produced by the metabolically active cells of seeds, and apparently play important roles in biological processes such as germination and dormancy. Germination and ROS accumulation appear to be linked, and seed germination success may be closely associated with internal ROS contents and the activities of ROS-scavenging systems. Although ROS were long considered hazardous molecules, their functions as cell signaling compounds are now well established and widely studied in plants. In seeds, ROS have important roles in endosperm weakening, the mobilization of seed reserves, protection against pathogens, and programmed cell death. ROS may also function as messengers or transmitters of environmental cues during seed germination. Little is currently known, however, about ROS biochemistry or their functions or the signaling pathways during these processes, which are to be considered in the present review.

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Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

Physiological Reviews ◽

10.1152/physrev.00026.2013 ◽

2014 ◽

Vol 94 (3) ◽

pp. 909-950 ◽

Cited By ~ 1195

Author(s):

Dmitry B. Zorov ◽

Magdalena Juhaszova ◽

Steven J. Sollott

Keyword(s):

Reactive Oxygen Species ◽

Mitochondrial Permeability Transition ◽

Physiological Role ◽

Reactive Oxygen ◽

Anion Channel ◽

Oxygen Species ◽

Redox Stress ◽

Mitochondrial Ros

Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo.

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