Alterations in NO/ROS ratio and expression of Trx1 and Prdx2 in isoproterenol-induced cardiac hypertrophy Hao Su, Marco Pistolozzi, Xingjuan Shi, Xiaoou Sun, and Wen Tan Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China Acta Biochim Biophys Sin 2017, 49: 1022–1028; doi: 10.1093/abbs/gmx102 The dev elopment of cardiac hypertrophy is a complicated process, which undergoes a transition from compensatory hypertrophy to heart failure, and the identific ation of new biomarkers and targets for this disease is greatly needed. Here we investigated the development of isoproterenol (ISO)-induced cardiac hypertrophy in an in vitro experimental model. After the induction of hypertrophy with ISO treatment in H9c2 cells, cell surface area, cell viability, cellular reactive oxygen species (ROS), and nitric oxide (NO) levels were tested. Our data showed that the cell viability, mitochondrial membrane potential, and NO/ROS balance varied during the development of cardiac hypertrophy in H9c2 cells. It was also found that the expression of thioredoxin1 (Trx1) and peroxiredoxin2 (P rdx2) was decreased during the cardiac hypertrophy of H9c2 cells. These results suggest a critical role for Trx1 and Prdx2 in the cardiac hypertrophy of H9c2 cells and in the transition from compensated hypertrophy to de-compensated hypertrophy in H9c2 cells, and our findings may have important implications for the management of this disease. ISO results in an imbalance in NO/ROS ISO-induced cardiac hypertrophy is related to the expression of Trx1 and Prdx2 阅读原文: http://www.abbs.org.cn/arts.asp?id=4228 获取全文: abbs@sibs.ac.cn 相关论文: 1 Toll-Like Receptor 4 Inhibition Improves Oxidative Stress and Mitochondrial Health in Isoproterenol-Induced Cardiac Hypertrophy in Rats 2 SIRT6 suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy 3 Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity 4 L-arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric oxide and polyamine pathways 5 Requirement of nuclear factor-kappa B in angiotensin II- and isoproterenol-induced cardiac hypertrophy in vivo 6 Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition 7 Differential Regulation of Proteasome Function in Isoproterenol-Induced Cardiac Hypertrophy 8 Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice
活性氧 (ROS) 在植物的生长、发育和对外界生物和非生物环境刺激的反应及细胞程序性死亡等调控过程中是一个重要的信号分子。 植物在各种逆境下在细胞内产生的诸如氧化氮、单线态氧、过氧化氢等活性氧自由基对植物抗逆性调控因子的表达和细胞死亡调控具有重要意义。尽管过氧化氢（ H 2 O 2 ）能够促进一些植物的种子萌发，诸如拟南芥，大麦，小麦，水稻和向日葵等，然而这种种子萌发的机制仍不得而知。 Ishibashi 等（ 2013 ）用 H 2 O 2 和 N- 乙酰半胱氨酸分别处理大豆种子，发现 H 2 O 2 促进种子萌发， N- 乙酰半胱氨酸则抑制萌发，表明活性氧参与种子萌发的调控。 N- 乙酰半胱氨酸抑制乙烯合成相关的基因表达，并抑制内源乙烯的合成。乙烯利和 H 2 O 2 处理则可以逆转 N- 乙酰半胱氨酸的影响。 Ishibashi 等认为，大豆种子在吸胀以后，胚轴产生 ROS ，诱导内源乙烯的产生，促进根尖细胞的延长。 Yushi Ishibashi, Yuka Koda, Shao-Hui Zheng, Takashi Yuasa, and Mari Iwaya-Inoue Regulation of soybean seed germination through ethylene production in response to reactive oxygen species Ann Bot (2013) 111(1): 95-102 first published online November 6, 2012 doi:10.1093/aob/mcs240
我们实验室今年被接受发表的第8篇论文由 任长虹 完成。 GLB-13 is associated with oxidative stress resistance in Caenorhabditis elegans Changhong Ren 1,4 *, Yuan Li 1,2 *, Rongrong Han 1,2 *, Dawen Gao 1 *, Weiguang Li 1 , Jinping Shi 1 , David Hoogewijs 3 , Bart P Braeckman 3 , Sasha De Henau 3 , Yiming Lu 1 , Wubin Qu 1 , Yan Gao 1 , Yonghong Wu 1 , Zhihui Li 1 , Huqi Liu 2 , Zhaoyan Wang 5 , Chenggang Zhang 1§ § Corresponding author: Chenggang Zhang, Beijing Institute of Radiation Medicine, Taiping Road 27, Beijing 100850, China. Tel/Fax: +86-10-68169574, E-mail: zhangcg@bmi.ac.cn Running title : GLB-13 associate with oxidative stress resistance Abstract Globins constitute a superfamily of heme-binding proteins that is widely present in many species. There are 33 putative globins in the genome of C. elegans , where glb-13 is a homolog of neuroglobin (Ngb) based on sequence analysis and specific expression in neurons. Here we examined whether glb-13 as well as Ngb is also associated with resistance to reactive oxygen species (ROS) induced by paraquat. Our results showed that the mRNA level of glb-13 was significantly upregulated after paraquat exposure. Expression of a GFP reporter gene directed by the glb-13 promoter was increased by paraquat exposure. The mutant C. elegans strain glb-13( tm2825) was sensitive to paraquat-induced oxidative stress. Overexpression of human Ngb (hNgb) in C. elegans neuronal cells can rescue the paraquat sensitive phenotype of the mutant strain. glb-13 mutation or hNgb overexpression did not affect the expression of antioxidant enzymes such as superoxide dismutase (SOD). To examine the ROS-scavenging capabilities of hNgb and glb-13 , we further examined the level of ROS in glb-13 mutant and hNgb transgenic (hNgb-Tg) worms. There was no statistical difference in ROS levels in the untreated controls, however in paraquat-treated worms, the ROS level was statistically repressed in the hNgb-Tg relative to enhanced green fluorescent protein (EGFP)-Tg worms or wildtype animals. Additionally, the ROS level of glb-13 mutant was statistically higher than the wildtype animals. Furthermore, hNgb overexpression diminished the ROS level of glb-13 mutant. In conclusion, hNgb can rescue the ROS sensitive phenotype of the glb-13 mutant strain. The protein GLB-13 seems to have an hNgb-like function, suggesting the importance of the globin protein family in maintaining the homeostasis of ROS signals. Our data provided evidence for the first time that glb-13 is associated with the resistance against oxidative stress-induced toxicity. Keywords: glb-13 ; neuroglobin; paraquat; ROS; transgenic; Caenorhabditis elegans
Reperfusion injury after myocardial infarction: The role of free radicals and the inflammatory response K.S. Kilgore a and B.R. Lucchesi , a a Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0626, USA Received 27 May 1993; revised 17 August 1993; accepted 17 August 1993. Available online 15 January 2003. Abstract Development of thrombolytic therapy as a treatment for myocardial infarction has focused attention on the events that occur upon reperfusion of ischemic myocardial tissue. Although it is well documented that salvage of the ischemic myocardium is dependent upon timely reperfusion, it is likely that the very events critical for survival may, in fact, lead to further tissue injury. A widely recognized source of reperfusion injury is the generation of oxygen -derived free radicals. These reactive oxygen species, which are formed within the first moments of reperfusion, are known to be cytotoxic to surrounding cells. In addition, strong support exists for the involvement of the inflammatory system in mediating tissue damage upon reperfusion. Coincident with the recruitment of neutrophils and activation of the complement system is an increase in the loss of viable cells. Although a number of mechanisms are likely to be involved in reperfusion injury, this discussion focuses on the roles that oxygen -derived free radicals and the inflammatory system play in mediating reperfusion injury. Keywords: adhesion molecules; complement; inflammation; membrane attack complex (MAC); myocardial ischemia; neutrophil; oxygen paradox; oxygen radical; reperfusion Reactive oxygen species may cause myocardial reperfusion injury This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Douglas A. Peterson a , b , c , Richard W. Asinger a , b , c , K. Joseph Elsperger a , b , c , David C. Homans a , b , c and John W. Eaton a , b , c a Division of Clinical Pharmacology, Veterans Administration Hospital Minneapolis, Minnesota, USA b Department of Medicine, Hennepin County Medical Center Minneapolis, Minnesota, USA c Department of Cardiology, Laboratory Medicine/Pathology, and Medicine, and Dight Institute for Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA Received 11 December 1984. Available online 4 May 2005. Summary The pathogenic mechanisms responsible for heart damage following temporary coronary artery occlusion are unknown. Some damage may be mediated by a normal cellular enzyme, xanthine dehydrogenase, which converts to xanthine oxidase during myocardial ischemia. Reperfusion, with restoration of oxygen supply, may then lead to formation of superoxide by xanthine oxidase, possibly initiating a cascade of oxidative events. In support of this, reperfusion of transiently ischemic canine myocardium leads to a rapid loss of cellular glutathione and a decrease in catalase activity, both indicative of enhanced generation of activated oxygen. Allopurinol-an inhibitor of xanthine oxidase ameliorates both biochemical damage and functional deficits ordinarily triggered by ischemia and reperfusion, suggesting one possible mode of pharmacologic intervention following acute myocardial infarction. Reperfusion injury after myocardial infarction: The role of free radicals and the inflammatory response This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. K.S. Kilgore a and B.R. Lucchesi , a a Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0626, USA Received 27 May 1993; revised 17 August 1993; accepted 17 August 1993. Available online 15 January 2003. Abstract Development of thrombolytic therapy as a treatment for myocardial infarction has focused attention on the events that occur upon reperfusion of ischemic myocardial tissue. Although it is well documented that salvage of the ischemic myocardium is dependent upon timely reperfusion, it is likely that the very events critical for survival may, in fact, lead to further tissue injury. A widely recognized source of reperfusion injury is the generation of oxygen -derived free radicals. These reactive oxygen species, which are formed within the first moments of reperfusion, are known to be cytotoxic to surrounding cells. In addition, strong support exists for the involvement of the inflammatory system in mediating tissue damage upon reperfusion. Coincident with the recruitment of neutrophils and activation of the complement system is an increase in the loss of viable cells. Although a number of mechanisms are likely to be involved in reperfusion injury, this discussion focuses on the roles that oxygen -derived free radicals and the inflammatory system play in mediating reperfusion injury. Keywords: adhesion molecules; complement; inflammation; membrane attack complex (MAC); myocardial ischemia; neutrophil; oxygen paradox; oxygen radical; reperfusion Stem Cell Therapy for the Treatment of Acute Myocardial Infarction This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Jonathan H. Dinsmore PhD a and Nabil Dib MD, MSc b , c , , a Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA b Cardiovascular Research, Catholic Health Care West (CHW), Mercy Gilbert and Chandler Medical Centers, Phoenix, AZ 85297, USA c Clinical Cardiovascular Cell Therapy, San Diego Medical Center, University of California, San Diego, USA Available online 2 December 2009. The last decade has been accompanied by great optimism and interest in the concept of cell or tissue regeneration in the postinfarction myocardium . However, despite the promise, progress was slow. Data derived from multiple controlled studies in hundreds of patients postmyocardial infarction have shown hints of potential benefit but not of the magnitude anticipated. The complexity and hurdles to repair the damaged myocardium have been more daunting than originally estimated. In the end analysis, progress will be made incrementally. The promise for cell therapy continues to be significant, but so are the challenges ahead. This article takes a fresh look at the progress in myocardial regeneration. The authors look at the postmyocardial environment for cues that may guide repair and they look closely atthe clinical data for evidence of cardiac regeneration. This evidence is used for suggestions on how to best proceed with future work. Keywords: Stem cell ; Myocardial infarction ; Therapy; Myocardial regeneration Reactive oxygen species may cause myocardial reperfusion injury This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Douglas A. Peterson a , b , c , Richard W. Asinger a , b , c , K. Joseph Elsperger a , b , c , David C. Homans a , b , c and John W. Eaton a , b , c a Division of Clinical Pharmacology, Veterans Administration Hospital Minneapolis, Minnesota, USA b Department of Medicine, Hennepin County Medical Center Minneapolis, Minnesota, USA c Department of Cardiology, Laboratory Medicine/Pathology, and Medicine, and Dight Institute for Human Genetics, University of Minnesota, Minneapolis, Minnesota, USA Received 11 December 1984. Available online 4 May 2005. Summary The pathogenic mechanisms responsible for heart damage following temporary coronary artery occlusion are unknown. Some damage may be mediated by a normal cellular enzyme, xanthine dehydrogenase, which converts to xanthine oxidase during myocardial ischemia. Reperfusion, with restoration of oxygen supply, may then lead to formation of superoxide by xanthine oxidase, possibly initiating a cascade of oxidative events. In support of this, reperfusion of transiently ischemic canine myocardium leads to a rapid loss of cellular glutathione and a decrease in catalase activity, both indicative of enhanced generation of activated oxygen. Allopurinol-an inhibitor of xanthine oxidase ameliorates both biochemical damage and functional deficits ordinarily triggered by ischemia and reperfusion, suggesting one possible mode of pharmacologic intervention following acute myocardial infarction. Reperfusion injury after myocardial infarction: The role of free radicals and the inflammatory response This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. K.S. Kilgore a and B.R. Lucchesi , a a Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0626, USA Received 27 May 1993; revised 17 August 1993; accepted 17 August 1993. Available online 15 January 2003. Abstract Development of thrombolytic therapy as a treatment for myocardial infarction has focused attention on the events that occur upon reperfusion of ischemic myocardial tissue. Although it is well documented that salvage of the ischemic myocardium is dependent upon timely reperfusion, it is likely that the very events critical for survival may, in fact, lead to further tissue injury. A widely recognized source of reperfusion injury is the generation of oxygen -derived free radicals. These reactive oxygen species, which are formed within the first moments of reperfusion, are known to be cytotoxic to surrounding cells. In addition, strong support exists for the involvement of the inflammatory system in mediating tissue damage upon reperfusion. Coincident with the recruitment of neutrophils and activation of the complement system is an increase in the loss of viable cells. Although a number of mechanisms are likely to be involved in reperfusion injury, this discussion focuses on the roles that oxygen -derived free radicals and the inflammatory system play in mediating reperfusion injury. Keywords: adhesion molecules; complement; inflammation; membrane attack complex (MAC); myocardial ischemia; neutrophil; oxygen paradox; oxygen radical; reperfusion Myocardial injury mediated by oxygen free radicals This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. John T. Flaherty M.D. Cardiology Division, Johns Hopkins Hospital, Baltimore, Maryland, USA Available online 1 June 2004. Abstract Increasing evidence suggests that oxygen free radicals play a major role in the pathogenesis of reperfusion injury. Initial indirect evidence was based on beneficial effects of free radical scavengers administered exogenously at the time of postischemic reperfusion. Recent electron paramagnetic resonance (EPR) spectroscopy studies show a burst of oxygen -centered free radical generation during the first 60 seconds of reflow and administration of either a free radical scavenger, such as superoxide dismutase (SOD), or an iron chelator, such as deferoxamine, prevents this burst. The in vitro data obtained in a perfused rabbit heart model and the impressive reduction in infarct size, shown in an intact canine model, suggest that well-designed, randomized, placebo-controlled clinical trials of free radical scavengers and/or antioxidants should be performed to determine if postischemic reperfusion injury can be shown and/or prevented in humans. Mitochondrial Pathophysiology, Reactive Oxygen Species, and Cardiovascular Diseases This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Ling Gao MD, PhD a , b , Karine Laude PhD c and Hua Cai MD, PhD a , b , , a Division of Molecular Medicine, Department of Anesthesiology, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA b Division of Molecular Medicine, Department of Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA c FORENAP Pharma, 27 Rue du 4me RSM, BP 27, 68250 Rouffach, France Available online 1 February 2008. This article discusses mitochondrial pathophysiology, reactive oxygen species, and cardiovascular diseases. Mitochondrial respiratory chains are responsible for energy metabolism/ATP production through the tricyclic antidepressant cycle, coupling of oxidative phosphorylation, and electron transfer. The mitochondrion produces reactive oxygen species as side products of respiration. The mitochondrial derived reactive oxygen species is involved in the pathogenesis of various clinical disorders including heart failure, hypoxia, ischemia/reperfusion injury, diabetes, neurodegenerative diseases, and the physiologic process of aging. Observational and mechanistical studies of these pathologic roles of mitochondria are discussed in depth in this article. Oxygen free radicals and myocardial reperfusion injury This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. MDRichard C Dart and MDArthur B Sanders Section of Emergency Medicine, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona, USA Received 30 March 1987; revised 12 August 1987; accepted 30 September 1987. Available online 27 April 2005. Diseases involving tissue reperfusion following ischemia are gaining significance in emergency medicine. The significance of reperfusion injury and the probable role of oxygen -derived free radicals has been described in many tissues, particularly the heart. During myocardial reperfusion a burst of oxygen -derived free radicals overwhelms normal cellular defenses. These radicals may have several detrimental effects. They can oxidize lipids, leading to membrane dysfunction. They can also alter nucleic and other proteins. Cellular dysfunction and death may ensue. Prevention of oxygen -derived free radical injury appears possible and may be feasible for several disease processes, including myocardial reperfusion after infarction. Author Keywords: injury, reperfusion, myocardial ; radicals, oxygen free, myocardial Mechanisms of myocardial reperfusion injury This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. James L. Park PhD a and Benedict R. Lucchesi PhD, MD , , a a Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA Available online 19 November 1999. Abstract Reperfusion of the ischemic myocardium results in irreversible tissue injury and cell necrosis , leading to decreased cardiac performance. While early reperfusion of the heart is essential in preventing further tissue damage due to ischemia , reintroduction of blood flow can expedite the death of vulnerable, but still viable, myocardial tissue, by initiating a series of events involving both intracellular and extracellular mechanisms. In the last decade, extensive efforts have focused on the role of cytotoxic reactive oxygen species, complement activation , neutrophil adhesion, and the interactions between complement and neutrophils during myocardial reperfusion injury. Without reperfusion, myocardial cell death evolves slowly over the course of hours. In contrast, reperfusion after an ischemic insult of sufficient duration initiates an inflammatory response , beginning with complement activation , followed by the recruitment and accumulation of neutrophils into the reperfused myocardium . Modulation of the inflammatory response , therefore, constitutes a potential pharmacological target to protect the heart from reperfusion injury. Recognition of the initiating factor(s) involved in myocardial reperfusion injury should aid in development of pharmacological interventions to selectively or collectively attenuate the sequence of events that mediate extension of tissue injury beyond that caused by the ischemic insult. Review article Reperfusion injury This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. John T. Flaherty * , a and Myron L. Weisfeldt ** , a a Department of Medicine, Johns Hopkins Hospital, Clayton Heart Center, Baltimore, MD 21205, U.S.A. Received 4 April 1988; revised 7 July 1988; accepted 7 July 1988. Available online 15 January 2003. Abstract Several lines of evidence point to a major role of oxygen free radicals in the pathogenesis of cell death or dysfunction in a variety of disease processes. Recent studies from this as well as other laboratories have demonstrated that oxygen free radicals play a major role in the pathogenesis of post-ischemic reperfusion injury in the heart. 14 We have recently developed methods for direct measurement of radical species and/or specific byproducts of radical injury. 5 Timely administration of oxygen radical scavengers reduced the quantity of free radicals generated following reperfusion and in addition improved recovery of post-ischemic ventricular function and metabolism. 3,6 In a regionally ischemic model the free radical scavenger recombinant human superoxide dismutase also administered at the time of reflow was shown to limit infarct size. 4 In this article we review the biophysical and molecular mechanisms of oxygen free radical generation that are viewed as contributing to post-ischemic reperfusion injury. We also discuss the mechanisms by which the body defends against free radical attack and the interrelationship of free radical injury to other mechanisms of tissue injury. Keywords: Myocardial reperfusion injury; Oxygen free radicals; Superoxide radicals; Hydroxyl radicals; Free radical scavengers; Superoxide dismutase Myocardial reperfusion injury: Role of oxygen radicals and potential therapy with antioxidants *1 This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Mohamed O. Jeroudi MD , , Craig J. Hartley PhD and Roberto Bolli MD From the Section of Cardiology, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, U.S.A. Available online 22 April 2004. Abstract Experimental studies have demonstrated that reperfusion is associated with a host of distinctive pathophysiologic derangements, the most important of which are reperfusion arrhythmias, transient mechanical dysfunction or myocardial stunning, and cell death. Reperfusion arrhythmias and myocardial stunning occur in experimental animals after transient ischemia followed by reperfusion, and there is considerable evidence that these derangements also develop in humans, although the existence of malignant reperfusion arrhythmias in humans remains uncertain. Reperfusion arrhythmias and myocardial stunning can be considered manifestations of sublethal, reversible cellular injury. The pathogenesis of reperfusion arrhythmias and stunning has not been conclusively established; however, there is considerable evidence that generation of oxygen radicals and perturbations of calcium homeostasis play an important role. Antioxidants and calcium antagonists have been shown to mitigate these manifestations of reperfusion injury. In contrast, the likelihood of lethal reperfusion-induced injury remains highly controversial. Although many studies have reported reduction of infarct size with antioxidants, numerous others have failed to reproduce these results. Consequently, intense controversy persists regarding whether oxygen radicals contribute to extending cell death following reperfusion and whether reperfusion itself causes cell death. Neither the resolution of this controversy nor the availability of clinical therapies to reduce reperfusion-induced cell death is likely in the near future. Review article Free radicals and the heart This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. N. Kaul a , b , c , N. Siveski-Iliskovic a , b , c , M. Hill a , b , c , J. Slezak a , b , c and P.K. Singal , a , b , c a Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada b Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada c Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia Received 2 June 1993; accepted 2 July 1993. Available online 18 November 2002. Abstract Because of the molecular configuration, most free radicals are highly reactive and can cause cell injury. Protective mechanisms have evolved to provide defense against freeradical injury. Any time these defense systems are overwhelmed, such as during disease states, cell dysfunction may occur. In this review we discuss cellular sources as well as the significance of free radicals, oxidative stress, and antioxidants. A probable role of oxidative stress in various cardiac pathologies has been also analyzed. Although some methods for the detection of free radicals as well as oxidative stress have been cited, better methods to study the quantity as well as subcellular distribution of free radicals are needed in order to understand fully the role of free radicals in both health and disease. Keywords: Oxidative Stress; Cardiac pathologies; Antioxidants; Myocardial dysfunction Free radicals in ischemic myocardial injury This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Steven W. Werns M.D. a , Michael J. Shea M.D. a and Benedict R. Lucchesi M.D., Ph.D. b , a Department of Internal Medicine (Division of Cardiology) The University of Michigan Medicine School, Ann Arbor, Michigan 48109, U.S.A. b Department of Pharmacology The University of Michigan Medicine School, Ann Arbor, Michigan 48109, U.S.A. Received 23 January 1985; revised 11 March 1985; accepted 12 March 1985.; Available online 19 December 2002. Abstract Myrocardial ischemia causes release of chemotactic factors, migration of neutrophils, peroxidation of lipids, and depletion of free radical scavengers. The invading neutrophils may injure the myrocardial vasculature and sarcolemma by generating oxygen free radicals. Several agents that affect neutrophils or oxygen radicals were evaluated in a canine model of regional myocardial ischemia and reperfusion. Anesthetized dogs underwent occlusion and reperfusion of the left circumflex coronary artery. Infarct zone, area at risk infarction, and total left ventricle were quantified by gravimetric and planimetric analysis. Limitation of infarct size by ibuprofen was associated with marked suppression of leukocyte accumulation within the ischemic myocardium. Neutrophil depletion by antiserum resulted in similar reductions of infarct size and was accompanied by a reduction in leukocyte infiltration. A combination of oxygen radical scaverngers, superoxide dismutase plus catalase, decreased myocardial injury whether infusion began before occlusion or 75 min after occlusion. None of the treatments significantly altered hemodynamic indices of myocardial oxygen demand. Reduction of infarct size by ibuprofen, neutrophil antiserum, and free radical scavengers indicates that neutrophils and oxygen radicals participate in producing the irreversible damage to the myocardium during ischemia and reperfusion. Author Keywords: Superoxide dismutase; Catalase; Reperfusion injury; Myocardial ischemia; Polymorphonuclear neutrophils; Oxygen free radicals; Free radical scavengers; Ibuprofen Nitric Oxide and Cardiac Remodeling This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Jonathan Passeri MD and Kenneth D. Bloch MD , Massachusetts General Hospital, Charlestown, MA, USA Available online 21 July 2005. Cardiac remodeling occurs as an adaptive response to chronic increases in hemodynamic load and neurohormonal stimulation but may become maladaptive over time, leading to deleterious structural and functional alterations and manifesting clinically as congestive heart failure. On a cellular level, cardiac myocyte hypertrophy and apoptosis, fibroblast proliferation, and changes in the extracellular matrix are some of the principal alterations underlying the remodeling process. In recent years, nitric oxide (NO) has been recognized to modulate contractile function, myocardial oxygen metabolism, ventricular hypertrophy and apoptosis, and fibrosis. The identification of the different isoforms of NO synthase and the generation of genetically modified mice lacking or overexpressing these enzymes have provided new insights into the complexity of NO biology and its multifaceted role in cardiac remodeling and heart failure. Cardiac remodeling occurs as an adaptive response to chronic increases in hemodynamic load and neurohormonal stimulation but may become maladaptive over time, leading to deleterious structural and functional alterations and manifesting clinically as congestive heart failure. On a cellular level, cardiac myocyte hypertrophy and apoptosis, fibroblast proliferation, and changes in the extracellular matrix are some of the principal alterations underlying the remodeling process. In recent years, nitric oxide (NO) has been recognized to modulate contractile function, myocardial oxygen metabolism, ventricular hypertrophy and apoptosis, and fibrosis. The identification of the different isoforms of NO synthase and the generation of genetically modified mice lacking or overexpressing these enzymes have provided new insights into the complexity of NO biology and its multifaceted role in cardiac remodeling and heart failure. 17- Reactive Oxygen: Recent Therapeutic Intervention Strategies This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Jill A. Panetta a and John M. McCall b a The Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA b Discovery Research, The Upjohn Company, Kalamazoo, Michigan 49001, USA Available online 2 August 2007. Summary This review generally describes the injury mosaic of ischemia-reperfusion injury and then discusses the role of reactive oxygen in that process. The ischaemia-reperfusion injury process is characterized by metabolic and ionic changes, protease activation, changes in the arachidonic acid cascade, lipid peroxidation and inflammatory injury. Figure 17.1 gives a comprehensive overview of the complete injury cascade. Not surprisingly, an injury cascade as complex as that described in Fig. 17.1 has invited many therapeutic interventions. Calcium channel blockers, NMDA antagonists, lipid peroxidation inhibitors, diuretics, iron chelators, magnesium, opiate antagonists, anti-inflammatories and more have all been tried with varied success in models of central nervous system (CNS) injury. This review emphasizes the therapeutic role of compounds that modulate reactive oxygen -mediated injury. Injury processes in the CNS are also emphasized. Our review is organized into the following sections: Introduction, Enzyme-related therapeutic approaches, Enzymatic antioxidants/derivatives, Exogenous antioxidants and the Inflammatory cascade. Structures of new compounds are usually included in the text. We have concentrated on the recent literature. Reperfusion injury in the ischemic myocardium This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Renu Virmani MD a , , Frank D. Kolodgie MS a , Mervyn B. Forman MD, PhD * , Andrew Farb MD a and Russell M. Jones a a From the Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC, USA * Department of Cardiology, Vanderbilt University, Nashville, Tennessee, USA Received 18 April 1991; accepted 7 October 1991. Available online 28 April 2004. Abstract Myocardial reperfusion injury is defined as the conversion of reversibly injured myocytes to irreversibly injured cells following temporary coronary artery occlusion. Although not universally accepted, the concept of lethal reperfusion injury is strongly supported by studies that temporally link an interventional therapy administered in the perireperfusion period to myocardial salvage. Myocardial reperfusion may be due to the deleterious consequences of cellular edema, calcium overload, free-radical generation, neutrophil infiltration, and microvascular damage. Current studies suggest that perfluorochemicals and adenosine (agents that preserve endothelium and attenuate neutrophil chemotaxis) are the most promising compounds that reduce infarct size in experimental animal models and may warrant clinical trials in man. This work was supported in part from funding provided by the American Registry of Pathology, Washington, DC.The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army, Navy, or Department of Defense.
（1）原理：DCFH-DA本身没有荧光，可以自由穿过细胞膜，进入细胞内后，可以被细胞内的酯酶水解生成DCFH。而DCFH不能通透细胞膜，从而使探针很容易被装载到细胞内。细胞内的活性氧可以氧化无荧光的DCFH生成有荧光的DCF。检测 DCF的荧光就可以知道细胞内活性氧的水平。 （2）材料与仪器 DCFH-DA购自Sigma公司，分子量487，用DMSO溶解，4.87 mg/ml 配成10 Mm，终浓度稀释成25M; FLUOstarOPTIMA 酶标仪。 （3）步骤 ① 接种细胞：96孔板，接种细胞数为每孔1.5万个细胞。 ② DCFH-DA孵育：接种24小时后用有糖earles 液洗两遍，并换上终浓度为25M DCFH-DA培养箱孵育30 min. ③ 处理：DCFH-DA孵育结束后，用有糖earles 液洗两遍给予处理（氧化应激或药物）。 ④ 检测： FLUOstarOPTIMA 酶标仪检测荧光， 488nm 激发波长， 525nm发射波长 。 （4）注意点 ① 要有无DCFH-DA孵育的对照； ② 多次清洗，注意操作规范，不要将细胞洗掉。 ③ 如果处理4小时以内，可以先孵育荧光染料，再处理后检测；如果处理超过4小时，建议先处理，再孵育染料检测。
标签: ROS
