S-nitrosylation of TRIM72 mends the broken heart: a molecular modifier-mediated cardioprotection.
Ontology highlight
ABSTRACT:
SUBMITTER: X'avia Chan CY
PROVIDER: S-EPMC4836859 | biostudies-literature | 2014 Jul
REPOSITORIES: biostudies-literature
Publications
S-nitrosylation of TRIM72 mends the broken heart: a molecular modifier-mediated cardioprotection.
X'avia Chan C Y CY Wang Ding D Cadeiras Martin M Deng Mario C MC Ping Peipei P
Journal of molecular and cellular cardiology 20140413
Similar Datasets
Project description:Homeostatic control of tissue oxygenation is achieved largely through changes in blood flow that are regulated by the classic physiological response of hypoxic vasodilation. The role of nitric oxide (NO) in the control of blood flow is a central tenet of cardiovascular biology. However, extensive evidence now indicates that hypoxic vasodilation entails S-nitrosothiol-based (SNO-based) vasoactivity (rather than NO per se) and that this activity is conveyed substantially by the ?Cys93 residue in hemoglobin. Thus, tissue oxygenation in the respiratory cycle is dependent on S-nitrosohemoglobin. This perspective predicts that red blood cells (RBCs) may play an important but previously undescribed role in cardioprotection. Here, we have found that cardiac injury and mortality in models of myocardial infarction and heart failure were greatly enhanced in mice lacking ?Cys93 S-nitrosylation. In addition, ?Cys93 mutant mice exhibited adaptive collateralization of cardiac vasculature that mitigated ischemic injury and predicted outcomes after myocardial infarction. Enhanced myopathic injury and mortality across different etiologies in the absence of ?Cys93 confirm the central cardiovascular role of RBC-derived SNO-based vasoactivity and point to a potential locus of therapeutic intervention. Our findings also suggest the possibility that RBCs may play a previously unappreciated role in heart disease.
| S-EPMC5127672 | biostudies-literature
Project description:Hydrogen sulfide (H2S), as a gaseous signalling molecule, has been found to play important roles in postconditioning (PostC)-induced cardioprotection. Similar to nitric oxide (NO)-mediated protein S-nitrosylation (SNO), recent studies suggest that H2S could regulate protein function through another redox-based post-translational modification on protein cysteine residue(s), i.e. S-sulfhydration (SSH). In this study, we examined whether there are changes in protein SSH associated with cardioprotection induced by treatment with H2S on reperfusion. In addition, we also examined whether there is cross talk between H2S and NO. Compared with control, treatment on reperfusion with NaHS (H2S donor, 100 µmol/L) significantly reduced post-ischaemic contractile dysfunction and infarct size. A comparable cardioprotective effect could be also achieved by reperfusion treatment with SNAP (NO donor, 10 µmol/L). Interestingly, simultaneous reperfusion with both donors had an additive protective effect. In addition, C-PTIO (NO scavenger, 20 µmol/L) eliminated the protection induced by NaHS and also the additive protection by SNAP + NaHS together. Using a modified biotin switch method, we observed a small increase in SSH following NaHS treatment on reperfusion. We also found that NaHS treatment on reperfusion increases SNO to a level comparable to that with SNAP treatment. In addition, there was an additive increase in SNO but not SSH when SNAP and NaHS were added together at reperfusion. Thus, part of the benefit of NaHS is an increase in SNO, and the magnitude of the protective effect is related to the magnitude of the increase in SNO.
| S-EPMC4798049 | biostudies-literature
Project description:BackgroundIt has been shown that the activation of estrogen receptor-beta (ER-beta) plays an important cardioprotective role against ischemia/reperfusion injury. However, the mechanism for this protection is not clear. We hypothesize that estrogen protects by ER-beta activation, which leads to S-nitrosylation (SNO) of key cardioprotective proteins.Methods and resultsWe treated ovariectomized C57BL/6J mice with the ER-beta selective agonist 2,2-bis(4-hydroxyphenyl)-proprionitrile (DPN), 17beta-estradiol (E2), or vehicle using Alzet minipumps for 2 weeks. Isolated hearts were Langendorff perfused and subjected to ischemia and reperfusion. Compared with vehicle-treated hearts, DPN- and E2-treated hearts had significantly better postischemic functional recovery and decreased infarct size. To test the specificity of DPN, we treated ER-beta-knockout mice with DPN. However, no cardioprotective effect of DPN was found in ER-beta-knockout mice, indicating that the DPN-induced cardioprotection occurs through the activation of ER-beta. Using DyLight-maleimide fluors and a modified biotin switch method, we used a 2-dimensional DyLight fluorescence difference gel electrophoresis proteomic method to quantify differences in SNO of proteins. DPN- and E2-treated hearts showed an increase in SNO of a number of proteins. Interestingly, many of these proteins also had been shown to have increased SNO in preconditioned hearts. In addition, the DPN-induced cardioprotection and increased SNO were abolished by treatment with a nitric oxide synthase inhibitor.ConclusionsThe activation of ER-beta by DPN treatment leads to increased protein SNO and cardioprotection against ischemia/reperfusion injury, suggesting that long-term estrogen exposure protects hearts largely via activation of ER-beta and nitric oxide/SNO signaling.
| S-EPMC2778304 | biostudies-literature
Project description: Not available
| S-EPMC2679833 | biostudies-literature
Project description:Advanced heart failure is often accompanied by perturbations in cardiac chamber or valve geometries which result in worsening cardiac function and hemodynamics. Once limited to surgical procedures, recent developments in minimally invasive percutaneous techniques have demonstrated efficacy in patients with both reduced and preserved ejection fraction who are at an elevated surgical risk for perioperative events. This review highlights a subset of the interventions available in clinical practice or in development for the treatment of these valvular and structural alterations.
| S-EPMC10179306 | biostudies-literature
Project description:The aim of this study was to determine whether thioredoxin 1 (Trx1) mediates the cardioprotective effects of hydrogen sulfide (H2S) in a model of ischemic-induced heart failure (HF).Mice with a cardiac-specific overexpression of a dominant negative mutant of Trx1 and wild-type littermates were subjected to ischemic-induced HF. Treatment with H2S as sodium sulfide (Na2S) not only increased the gene and protein expression of Trx1 in the absence of ischemia but also augmented the HF-induced increase in both. Wild-type mice treated with Na2S experienced less left-ventricular dilatation, improved left-ventricular function, and less cardiac hypertrophy after the induction of HF. In contrast, Na2S therapy failed to improve any of these parameters in the dominant negative mutant of Trx1 mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na2S therapy inhibited HF-induced apoptosis signaling kinase-1 signaling and nuclear export of histone deacetylase 4 in a Trx1-dependent manner.These findings provide novel information that the upregulation of Trx1 by Na2S therapy in the setting of HF sets into motion events, such as the inhibition of apoptosis signaling kinase-1 signaling and histone deacetylase 4 nuclear export, which ultimately leads to the attenuationof left-ventricular remodeling.
| S-EPMC3827725 | biostudies-literature
Project description:Mesenchymal stem cell (MSC) exosomes may limit cardiac injury, and even reverse cardiac damage in animal models of ischemia. To understand exosome-mediated improvement in cardiac function we examined the proteomic alternations in the MSC exosome-treated mice hearts subjected to left coronary artery (LCA) ligation, with particular emphasis on peri-infarct areas. At 7 days after LCA ligation, left ventricular end systolic thickness, infarct size and survival of mice were studied. Mass spectrometric analysis of infarct and peri-infarct areas was carried out. Expression of inflammatory markers (LOX-1 and NLRP3) and cell death markers (Bax, Bcl-2, Caspases 1 and 3 and GSDMD) were investigated by Western blots and immunofluorescence. Proteomic analysis of the infarct and peri-infarct areas in saline-treated hearts revealed differentially expressed proteins involved in inflammation and apoptotic cell death, while showing depletion of processes governing cell death. Exosome treatment significantly improved the proteomic profile in both infarct and peri-infarct areas, more so in the peri-infarct areas. The infarct size was smaller (9 ± 1%), and cardiac contractile function (fractional shortening) was preserved in the exosome-treated mice (28 ± 2%). Survival of exosome-treated mice was also better. White blood cell accumulation in and around the infarct area, expression of LOX-1 and NLRP3 inflammasome, and markers of cell death (cleaved Caspase-3, Caspase-1, GSDMD, Bcl-2 and Bax) were dramatically reduced by MSC exosome treatment (all p < 0.01). In cultured primary mouse cardiomyocytes, treatment with MSC exosomes essentially reversed inflammation-induced pro-apoptotic and inflammatory signals (p < 0.01). MSC exosomes exert their cardioprotective effects by suppressing inflammation and pro-apoptotic processes, particularly in the peri-infarct areas, resulting in preservation of cardiac function after LCA ligation.
| S-EPMC8186026 | biostudies-literature
Project description:The urocortin (UCN) hormones UCN1 and UCN2 have been shown previously to confer significant protection against myocardial ischaemia/reperfusion (I/R) injury; however, the molecular mechanisms underlying their action are poorly understood. To further define the transcriptional effect of UCNs that underpins their cardioprotective activity, a microarray analysis was carried out using an in vivo rat coronary occlusion model of I/R injury. Infusion of UCN1 or UCN2 before the onset of reperfusion resulted in the differential regulation of 66 and 141 genes respectively, the majority of which have not been described previously. Functional analysis demonstrated that UCN-regulated genes are involved in a wide range of biological responses, including cell death (e.g. X-linked inhibitor of apoptosis protein), oxidative stress (e.g. nuclear factor erythroid derived 2-related factor 1/nuclear factor erythroid derived 2-like 1) and metabolism (e.g. Prkaa2/AMPK). In addition, both UCN1 and UCN2 were found to modulate the expression of a host of genes involved in G-protein-coupled receptor (GPCR) signalling including Rac2, Gnb1, Dab2ip (AIP1), Ralgds, Rnd3, Rap1a and PKA, thereby revealing previously unrecognised signalling intermediates downstream of CRH receptors. Moreover, several of these GPCR-related genes have been shown previously to be involved in mitogen-activated protein kinase (MAPK) activation, suggesting a link between CRH receptors and induction of MAPKs. In addition, we have shown that both UCN1 and UCN2 significantly reduce free radical damage following myocardial infarction, and comparison of the UCN gene signatures with that of the anti-oxidant tempol revealed a significant overlap. These data uncover novel gene expression changes induced by UCNs, which will serve as a platform to further understand their mechanism of action in normal physiology and cardioprotection.
| S-EPMC3069736 | biostudies-literature
Project description:BackgroundMortality from myocardial infarction (MI) has been decreasing since the introduction of primary percutaneous intervention. Late complications still pose a dilemma, such as deterioration of left ventricle (LV) function, LV aneurysms, and LV thrombus formation. If not adequately managed in a timely manner, this can result in life-threatening consequences. Restoration of LV function by surgical resection of the infarcted LV wall is an option for a few complicated cases, with variable outcomes.Case summaryA 66-year-old man presented with dyspnoea 2 years after his initial MI, which was treated with a drug-eluting stent to his left circumflex artery. His Warfarin had been stopped after 6 months of treatment of a small LV thrombus, which was noted at the time of his initial infarction. His echocardiogram on admission demonstrated severe LV systolic impairment of 23% (which had deteriorated from 40%) with a giant true aneurysm of the basal to mid-lateral wall, which resembled a Valentine heart. The presence of a large, organized thrombus filling the aneurysm complicated the case further. The patient underwent a resection of the LV aneurysm and thrombus. He remained asymptomatic and maintained a significant improvement of his LV function to 47% at his 5 months scan.DiscussionThe importance of imaging post-large MI and follow-up imaging once thrombus resolution has occurred is crucial. Patients with large LV aneurysm associated with severe refractory LV impairment and LV thrombus should be considered for LV aneurysmectomy for prognostic benefit and symptom relief.
| S-EPMC9382566 | biostudies-literature