Nitrosative stress and pharmacological modulation of heart failure

Pacher, Pál; Schulz, Richard; Liaudet, Lucas; Szabó, Csaba

doi:10.1016/j.tips.2005.04.003

Cited by 218 publications

(177 citation statements)

References 85 publications

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“…[1][2][3] Increased nitric oxide and superoxide, which can be also produced by resident macrophages (Kupffer cells) and infiltrating leukocytes (neutrophils) in alcohol-exposed animals, 2,3 can lead to the elevated production of peroxynitrite, which may cause cellular damage. 16,[34][35][36] In fact, the immunoblot results showed increased CD16, a marker protein for neutrophils, in the alcohol-exposed rats ( Supplementary Fig. 3), suggesting that neutrophil-derived oxidants may also contribute to oxidative inactivation of mitochondrial enzymes/proteins, leading to mitochondrial dysfunction and cellular damage.…”

Section: Discussionmentioning

confidence: 95%

“…Met, His, Trp, and Tyr) may also undergo modification under oxidative/nitrosative stress, potentially leading to inactivation and mitochondrial dysfunction (e.g., through reduced levels of ATP or accumulation of toxic aldehydes through inactivation of ATP synthase and ALDH2, respectively). 16,31,34 In the absence of proper management, these changes may ultimately contribute to alcohol-related cell/tissue damage.…”

Section: Discussionmentioning

confidence: 99%

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Inactivation of oxidized and S -nitrosylated mitochondrial proteins in alcoholic fatty liver of rats

et al. 2006

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Increased oxidative/nitrosative stress is a major contributing factor to alcohol-mediated mitochondrial dysfunction. However, which mitochondrial proteins are oxidatively modified under alcohol-induced oxidative/nitrosative stress is poorly understood. The aim of this study was to systematically investigate oxidized and/or S-nitrosylated mitochondrial proteins and to use a biotin-N-maleimide probe to evaluate their inactivation in alcoholic fatty livers of rats. Binge or chronic alcohol exposure significantly elevated nitric oxide, inducible nitric oxide synthase, and ethanol-inducible CYP2E1. The biotin-N-maleimide-labeled oxidized and/or S-nitrosylated mitochondrial proteins from pair-fed controls or alcohol-fed rat livers were subsequently purified with streptavidin-agarose. The overall patterns of oxidized and/or S-nitrosylated proteins resolved by 2-dimensional polyacrylamide gel electrophoresis were very similar in the chronic and binge alcohol treatment groups. Seventy-nine proteins that displayed differential spot intensities from those of control rats were identified by mass spectrometry. These include mitochondrial aldehyde dehydrogenase 2 (ALDH2), ATP synthase, acyl-CoA dehydrogenase, 3-ketoacyl-CoA thiolase, and many proteins involved in chaperone activity, mitochondrial electron transfer, and ion transport. The activity of 3-ketoacyl-CoA thiolase involved in mitochondrial ␤-oxidation of fatty acids was significantly inhibited in alcohol-exposed rat livers, consistent with hepatic fat accumulation, as determined by biochemical and histological analyses. Measurement of activity and immunoblot results showed that ALDH2 and ATP synthase were also inhibited through oxidative modification of their cysteine or tyrosine residues in alcoholic fatty livers of rats. In conclusion, our results help to explain the underlying mechanism for mitochondrial dysfunction and increased susceptibility to alcohol-mediated liver damage. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Inactivation of oxidized and S -nitrosylated mitochondrial proteins in alcoholic fatty liver of rats

et al. 2006

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“…In addition to HAT and HDACs, another family of chromatin modifying enzymes, called poly (ADP-ribose) polymerase (PARP), has been found to play a role in the development of cardiac hypertrophy and MHC gene regulation [107,134,135]. PARP1, a prototype member of the large PARP family, has been shown to interact with TEF1 to form a complex on M-CAT binding sites of the cardiac troponinT and MHC genes, leading to their muscle-specific gene regulation [136,137].…”

Section: Chromatin Modifying Enzymesmentioning

confidence: 99%

“…PARP1 has also been shown to control the activity of a member of the class-III HDACs (SIRT1), which has been shown to have an antihypertrophy potential, thus further indicating that PARP1 may have a role in the regulation of MHC isoform switch during hypertrophy [139,144]. The role of PARP1 in cardiac disorders and that of its co-regulators in gene regulation have recently been reviewed [134,145,146].…”

Section: Chromatin Modifying Enzymesmentioning

confidence: 99%

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

Gupta

2007

Journal of Molecular and Cellular Cardiology

190

171

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“…Superoxide anion, the primary precursor in ROS metabolic pathways, decreases NO bioavailability and attenuates vasodilatation, thus increasing cardiac loading in CHF. 32 NO is known to abolish mitochondrial oxidant damage and calcium overload, and reduce superoxide anion production via an efficient suppression on the activity of NAD(P)H oxidase and the assembly of NAD(P)H oxidase subunits. 1,33 Maintenance of NO levels is critical for recovery of heart failure after ischemic injury.…”

Section: Cardioprotection By Kallistatin Via Antioxidation L Gao Et Almentioning

confidence: 99%

Role of kallistatin in prevention of cardiac remodeling after chronic myocardial infarction

Gao

Yin

Smith

et al. 2008

Laboratory Investigation

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Oxidative stress causes cardiomyocyte death and subsequent ventricular dysfunction and cardiac remodeling after myocardial infarction (MI), thus contributing to high mortality in chronic heart failure patients. We investigated the effects of kallistatin in cardiac remodeling in a chronic MI rat model and in primary cardiac cells. Human kallistatin gene was injected intramyocardially 20 min after ligation of the left coronary artery. At 4 weeks after MI, expression of human kallistatin in rat hearts was identified by reverse transcription-polymerase chain reaction, immunohistochemistry and ELISA. Kallistatin administration improved cardiac performance, increased mean arterial pressure, decreased myocardial infarct size and restored left ventricular wall thickness. Kallistatin treatment significantly attenuated cardiomyocyte size and atrial natriuretic peptide expression. Kallistatin also reduced collagen accumulation, collagen fraction volume and expression of collagen types I and III, transforming growth factor-b1 (TGF-b1) and plasminogen activator inhibitor-1 in the myocardium. Inhibition of cardiac hypertrophy and fibrosis by kallistatin was associated with increased cardiac nitric oxide (NO) levels and decreased superoxide formation, NADH oxidase activity and p22-phox expression. Moreover, in both primary cultured rat cardiomyocytes and myofibroblasts, recombinant kallistatin inhibited intracellular superoxide formation induced by H 2 O 2 , and the antioxidant effect of kallistatin was abolished by No-nitro-L-arginine methyl ester (L-NAME), indicating a NO-mediated event. Kallistatin promoted survival of cardiomyocytes subjected to H 2 O 2 treatment, and inhibited H 2 O 2 -induced Akt and ERK phosphorylation, as well as NF-kB activation. Furthermore, kallistatin abrogated TGF-b-induced collagen synthesis and secretion in cultured myofibroblasts. This is the first study to demonstrate that kallistatin improves cardiac performance and prevents post-MI-induced cardiac hypertrophy and fibrosis through its antioxidant action. Myocardial infarction (MI) leads to cardiac remodeling with complex structural alterations. After an ischemic insult, left ventricle (LV) enlargement is followed by progressive diastolic stiffness, enhanced wall stress and oxygen consumption, thus resulting in cardiomyocyte hypertrophy, interstitial fibrosis and decreased cardiac output. Increased reactive oxygen species (ROS) levels are recognized to be involved in ischemic heart failure and considered to be a major cause of cardiomyocyte death, ventricular dysfunction and heart failure progress. 1 Under pathological conditions, increased oxidative stress damages DNA and mitochondrial function, activates proapoptotic signaling kinases and leads to myocyte apoptosis or necrosis. 2,3 Elevation of ROS activates a series of hypertrophic signaling kinases and transcription factors to stimulate cardiac hypertrophy. 3,4 Moreover, ROS stimulate fibroblast proliferation and activate the expression of profibrotic factors, including transforming growth...

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Nitrosative stress and pharmacological modulation of heart failure

Cited by 218 publications

References 85 publications

Inactivation of oxidized and S -nitrosylated mitochondrial proteins in alcoholic fatty liver of rats

Inactivation of oxidized and S -nitrosylated mitochondrial proteins in alcoholic fatty liver of rats

Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure

Role of kallistatin in prevention of cardiac remodeling after chronic myocardial infarction

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