Redox signaling in cardiovascular health and disease

Madamanchi, Nageswara R.; Runge, Marschall S.

doi:10.1016/j.freeradbiomed.2013.04.001

Cited by 183 publications

(154 citation statements)

References 563 publications

(600 reference statements)

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“…However, although antioxidants, such as co‐enzyme Q10, N‐acetylcysteine and vitamins C and E, have been reported to exert cardioprotective effects in experimental models (Sterba et al, 2013), the results of small randomized clinical trials have not shown clear benefit (van Dalen et al, 2011; Vincent et al, 2013). The lack of success of antioxidant therapeutic strategies is likely to demonstrate the complexity of redox reactions in biological tissues (Madamanchi and Runge, 2013), in which ROS are known to serve both physiological and maladaptive roles. It is likely, therefore, that selective targeting of particular sources of ROS or downstream effectors may represent a more viable approach.…”

Section: Introductionmentioning

confidence: 99%

Signalling mechanisms underlying doxorubicin and Nox2 NADPH oxidase‐induced cardiomyopathy: involvement of mitofusin‐2

McLaughlin

Zhao

O’Neill

et al. 2017

British J Pharmacology

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Background and PurposeThe anthracycline doxorubicin (DOX), although successful as a first‐line cancer treatment, induces cardiotoxicity linked with increased production of myocardial ROS, with Nox2 NADPH oxidase‐derived superoxide reported to play a key role. The aim of this study was to identify novel mechanisms underlying development of cardiac remodelling/dysfunction further to DOX‐stimulated Nox2 activation.Experimental ApproachNox2−/− and wild‐type (WT) littermate mice were administered DOX (12 mg·kg−1 over 3 weeks) prior to study at 4 weeks. Detailed mechanisms were investigated in murine HL‐1 cardiomyocytes, employing a robust model of oxidative stress, gene silencing and pharmacological tools.Key ResultsDOX‐induced cardiac dysfunction, cardiomyocyte remodelling, superoxide production and apoptosis in WT mice were attenuated in Nox2−/− mice. Transcriptional analysis of left ventricular tissue identified 152 differentially regulated genes (using adjusted P < 0.1) in DOX‐treated Nox2−/− versus WT mice, and network analysis highlighted ‘Cell death and survival’ as the biological function most significant to the dataset. The mitochondrial membrane protein, mitofusin‐2 (Mfn2), appeared as a strong candidate, with increased expression (1.5‐fold), confirmed by qPCR (1.3‐fold), matching clear published evidence of promotion of cardiomyocyte cell death. In HL‐1 cardiomyocytes, targeted siRNA knockdown of Nox2 decreased Mfn2 protein expression, but not vice versa. While inhibition of Nox2 activity along with DOX treatment attenuated its apoptotic and cytotoxic effects, reduced apoptosis after Mfn2 silencing reflected a sustained cytotoxic response and reduced cell viability.Conclusions and ImplicationsDOX‐induced and Nox2‐mediated up‐regulation of Mfn2, rather than contributing to cardiomyocyte dysfunction through apoptotic pathways, appears to promote a protective mechanism.Linked ArticlesThis article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc

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Section: Introductionmentioning

confidence: 99%

Signalling mechanisms underlying doxorubicin and Nox2 NADPH oxidase‐induced cardiomyopathy: involvement of mitofusin‐2

McLaughlin

Zhao

O’Neill

et al. 2017

British J Pharmacology

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“…Some factors are highly associated with heart failure in aging, such as oxidative stress and inflammation (Madamanchi and Runge 2013). Oxidative stress is due to metabolic function degradation causing reactive oxygen species (ROS) accumulation (Ahmed and Tang 2012).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts

Lin

Wei³

et al. 2014

AGE

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Exercise training is considered a benefit to heart function, but the benefit in aging hearts remains unknown. Activation of the PI3K-Akt survival pathway and suppression of Fas/FADD/caspase-8 apoptotic signaling by exercise training in hearts from young subjects have been described in our previous studies. However, the mechanisms are still unclear and need to be explored in aging hearts. Thus, 18-month-old rats were used as a model and underwent swimming exercise training, resveratrol treatment (15 mg/kg/day), or exercise training with resveratrol treatment for 1 month. The results showed that heart function in each group improved. AGE (2014) 36:9705

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“…However, ROS overproduction can further promote the inflammatory process and injure neighboring host cells and tissues by lipoperoxidation, proteolysis or DNA degradation (Braga et al, 2012;Mata-Campuzano et al, 2012;Tsumbu et al, 2011). Growing evidence suggests that an abnormal ROS production attributed to an absent regulation of PMNs respiratory burst is involved in the pathogenesis of various inflammatory disorders such as rheumatoid arthritis (Mirshafiey & Mohsenzadegan, 2008;Shah et al, 2011), atherosclerosis (Cheng et al, 2013;Ding et al, 2013), reperfusion injury (Gutowski & Kowalczyk, 2013;Madamanchi & Runge, 2013), and even cancer (Li et al, 2012). Thus, it is interesting to find antioxidative substances with the ability to inhibit ROS production and/or directly scavenge ROS formed in the process of respiratory burst.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of phenolic compounds fromArtocarpus styracifoliuson respiratory burst of rat neutrophils

Ren

Xiang²,

Hu³

et al. 2014

Pharmaceutical Biology

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Materials and methods:The anti-respiratory burst activities of eight phenolics (20 mM) were assessed by determining luminol-dependent chemiluminiscence in rat PMNs. Cytotoxicity of active compounds (1-1000 mM) was assayed by Trypan blue dye exclusion method. Cell-free models were employed to evaluate scavenging capacity of active compounds (20 mM) against reactive oxygen species.Results: The PMA-induced respiratory burst was significantly inhibited (p50.05) by six isoprenylated phenolics (AS1-6) at the concentration of 20 mM (below the toxic concentration) with the inhibition rate ranging from 25.0 to 99.6%. The inhibitory potency estimated by IC 50 was in the order of AS1 (3.1 mM) 4AS6 (5.9 mM) 4AS2 (9.1 mM) 4AS3 (10.0 mM) 4AS5 (29.7 mM) 4AS4 (57.7 mM). AS1-4, four isoprenylated flavones, potently quenched superoxide anion, hydroxyl radical, and hydrogen peroxide at the concentration of 20 mM with their scavenging rates in the range of 30.1-78.1%, 35.4-69.7%, and 65.5-86.3%, respectively. In contrast, AS5-6, two isoprenylated 2-arylbenzofurans, showed less effect than that exhibited by AS1-4. Conclusion and discussion: The isoprenylated phenolics from A. styracifolius can potently inhibit PMA-induced respiratory burst in rat neutrophils without showing cytotoxicity. The inhibitory effects of these isoprenylated phenolics on the respiratory burst might depend on their different types of structure.

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Redox signaling in cardiovascular health and disease

Cited by 183 publications

References 563 publications

Signalling mechanisms underlying doxorubicin and Nox2 NADPH oxidase‐induced cardiomyopathy: involvement of mitofusin‐2

Signalling mechanisms underlying doxorubicin and Nox2 NADPH oxidase‐induced cardiomyopathy: involvement of mitofusin‐2

Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts

Inhibitory effects of phenolic compounds fromArtocarpus styracifoliuson respiratory burst of rat neutrophils

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