NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair

Jiang, Fan; Zhang, Yun; Dusting, Gregory J.

doi:10.1124/pr.110.002980

Cited by 496 publications

(394 citation statements)

References 297 publications

(405 reference statements)

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“…Many reports showed that under the influence of some drug, increased cellular ROS generation induced cell death. 23) As a metabolite of the sulfur-containing amino acid, NAC was produced within the human and other mammal bodies. Its sulfhydryl group conferred antioxidant effects and the ability to reduce free radicals.…”

Section: Discussionmentioning

confidence: 99%

Hydroxyl Radical (·OH) Played a Pivotal Role in Oridonin-Induced Apoptosis and Autophagy in Human Epidermoid Carcinoma A431 Cells

Fan

Song

et al. 2012

Biological & Pharmaceutical Bulletin

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Oridonin, a diterpenoid compound extracted and purified from Rabdosia rubescen, has been reported to induce tumor cell apoptosis through tyrosine kinase pathway. To further examine the mechanism of oridonin, we selected human epidermoid carcinoma A431 cell as a test object. Besides apoptosis, oridonin also induced A431 cell autophagy, and this autophagy antagonized apoptosis and played a protective role for A431 cells. Reactive oxygen species (ROS) played a pivotal role in induction of cytotoxicity. Therefore, a ROS scavenger, N-acetylcysteine (NAC) combined with oridonin was appiled. Results of morphologic observation, flow cytometric analysis and Western blot analysis showed that NAC could significantly reverse both ROS generation and down-regulation of mitochondrial membrane potential in oridonin treated cells. NAC inhibited oridonin induced apoptosis through both the intrinsic and extrinsic apoptotic pathways. NAC effectively inhibited both oridonin-induced apoptosis and autophagy by reducing intracellular oxidative stress. To further examine the mechanism of ROS, exogenous enzyme antioxidants (superoxide dismutase (SOD), catalase (CAT)) and non-enzyme antioxidants (glutathione (GSH)) were applied to detect the effect of oridonin on ROS generation. Only GSH exerted a similar role with NAC, suggesting that hydroxyl radical (·OH) played the major role in oridonin-induced cell death. Oridonin could decrease the GSH level in A431 cells in a dosedependent manner. In addition, after treatment with ·OH donor, Fenton reagent, the changes in A431cells were similar to the results of oridonin treatment. All the results proved that ·OH played the pivotal role in oridonin induced apoptosis and autophagy in A431 cells.Key words oridonin; apoptosis; autophagy; reactive oxygen species; hydroxyl radical Reactive oxygen species (ROS) include highly reactive hydroxyl radicals (OH·), superoxide anions (O 2− ), singlet oxygen ( 1 O 2 ), and hydrogen peroxide (H 2 O 2 ), which form as natural products of the normal cellular metabolism of oxygen. 1) They play critical roles in the determination of cell fate by eliciting a wide variety of cellular responses, such as proliferation, differentiation and apoptosis.2) Under normal conditions, having been balanced by cell's antioxidant defense systems, low levels of ROS play important roles in cell signaling. However, under environmental stress, extended high levels of ROS would cause severe damage to cellular organisms, including DNA, RNA or proteins, which eventually lead to cell death via either apoptotic or other mechanisms.3) In many reports, ROS may also act as intracellular messengers, which are induced by a range of stimuli and triggered apoptosis. In these conditions, ROS are also produced in cell organelles, especially mitochondria. During oxidative stress-induced cell death, ROS can target the mitochondrial membrane potential. 4)Apoptosis (type I cell death) is one type of programmed cell death in multicellular organisms, and apoptotic cells are characterized by a series of mo...

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Section: Discussionmentioning

confidence: 99%

Hydroxyl Radical (·OH) Played a Pivotal Role in Oridonin-Induced Apoptosis and Autophagy in Human Epidermoid Carcinoma A431 Cells

Fan

Song

et al. 2012

Biological & Pharmaceutical Bulletin

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“…Nitrous oxide (N 2 O 3 ) is also a precursor of nitrous acid (HNO 2 ) as a result of its reaction with water. Nitrous acid (HNO 2 ) promotes deamination of DNA bases containing free NH 2 groups; for example, deamination of cytosine, adenine and guanine results in the formation of uracil, hypoxanthine and xanthine, respectively [27,29]. Nitric oxide (NO•) is not sufficiently reactive to attack DNA directly, but it can react with radical O 2 •-produced by phagocytes and generate peroxynitrite (ONOO-).…”

Section: Theoretical Backgroundmentioning

confidence: 99%

“…However, the concentration of these radicals may increase due to increased intracellular generation or deficiency of antioxidant mechanisms [26][27][28][29].…”

Section: Theoretical Backgroundmentioning

confidence: 99%

“…Phagocytes express a multicomponent enzyme complex called NADPH oxidase that catalyzes the electron reduction of O 2 . Finally, the radical O 2 •-can function as a molecular indicator due to its ability to oxidize -SH groups to disulfide bonds, which can activate and deactivate enzymes containing methionine [27]. OH• is the most deleterious ROS to organisms.…”

Section: Theoretical Backgroundmentioning

confidence: 99%

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The Association between Physical Exercise and Reactive Oxygen Species (ROS) Production

Silva¹

2015

J Sports Med Doping Stud

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The importance of exercise has been widely accepted by the public, professional organizations and the medical community, and the number of people around the world who practice day-to-day regular physical activity has recently increased. Physical activity is a primary requirement for the maintenance and promotion of health. However, intense exercise induces an increase in substrate utilization by the working muscles, resulting in an increased use of oxygen. This rise in oxygen consumption combined with the activation of specific metabolic pathways during or after exercise results in the generation of Reactive Oxygen Species (ROS). These substances are produced naturally by oxidative metabolic processes and are highly reactive. ROS can be useful in some situations; for example, macrophages use hydrogen peroxide to destroy bacteria. ROS increases during high-intensity exercise and its production is related to a large number of diseases, such as emphysema, inflammatory diseases, atherosclerosis, cancer and aging. During evolution, living organs developed an endogenous mechanism to minimize the damage caused by ROS, termed the antioxidant defense system. The imbalance between the production of ROS and the removal of these compounds by the antioxidant defense system causes a condition known as oxidative stress. This interesting paradox is exemplified by the hypothesis that physical exercises known to promote appropriate standards of health are also related to increased ROS production, which in turn closely correlate with various diseases. Recent publications have shown that ROS produced by exercise in adequate amounts may be linked to exercise benefits, both for health and for athletic performance. Thus, the aim of this article is to examine the close association between physical exercise and the production of ROS through an extensive literature review.

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“…defective proteins, and adaptation to high levels of ROS and resistance to ROS-dependent apoptosis -a common behaviour of all cancer cells (13). Many authors indicate that the oxidative stress is a direct or indirect result of ROSmediated damage on biological macromolecules and a major factor not only for carcinogenesis, but also for neurodegeneration, cardiovascular disease, inflammation, atherosclerosis, diabetes, aging, etc.…”

mentioning

confidence: 99%

Mitochondrial Dysfunction and Redox Imbalance as a Diagnostic Marker of “Free Radical Diseases”

2017

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NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair

Cited by 496 publications

References 297 publications

Hydroxyl Radical (·OH) Played a Pivotal Role in Oridonin-Induced Apoptosis and Autophagy in Human Epidermoid Carcinoma A431 Cells

Hydroxyl Radical (·OH) Played a Pivotal Role in Oridonin-Induced Apoptosis and Autophagy in Human Epidermoid Carcinoma A431 Cells

The Association between Physical Exercise and Reactive Oxygen Species (ROS) Production

Mitochondrial Dysfunction and Redox Imbalance as a Diagnostic Marker of “Free Radical Diseases”

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