Proteomic remodeling of proteasome in right heart failure

Fessart, Delphine; Martin‐Négrier, Marie‐Laure; Claverol, Stéphane; Thiolat, Marie-Laure; Crevel, Huguette; Toussaint, Christian; Bonneu, Marc; Müller, Bernard; Savineau, Jean-Pierre; Delom, Frédéric

doi:10.1016/j.yjmcc.2013.10.015

Cited by 22 publications

(19 citation statements)

References 56 publications

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“…Additionally, there are no models for studying RVR as most have focused on failure. One advantage of this model is most pronounced when compared with that of monocrotaline-induced animal models of chronic RVF [4,5] as the latter is not a reversible form of pressure-overload RVF. This precludes investigations into RVR and developing RV protective or RVR strategies.…”

Section: Discussionmentioning

confidence: 99%

Animal model of reversible, right ventricular failure

McKellar

Javan

Bowen

et al. 2015

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 99%

Animal model of reversible, right ventricular failure

McKellar

Javan

Bowen

et al. 2015

Journal of Surgical Research

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“…This analysis was performed by the proteomic facility of Bordeaux University (http://www.cgfb.u-bordeaux2.fr/en/synthese‐ proteome ). The steps of sample preparation and protein digestion, nano‐scale liquid chromatography‐tandem mass spectrometry analysis, and database search and results processing were performed as previously described (24). Label‐free quantitative data analysis was performed by using Progenesis Liquid Chromatography‐Tandem Mass Spectrometry 4.0 software (Nonlinear Dynamics, Newcastle, United Kingdom).…”

Section: Methodsmentioning

confidence: 99%

High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy

et al. 2016

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Podocytes play a key role in diabetic nephropathy pathogenesis, but alteration of their metabolism remains unknown in human kidney. By using a conditionally differentiating human podocyte cell line, we addressed the functional and molecular changes in podocyte energetics during in vitro development or under high glucose conditions. In 5 mM glucose medium, we observed a stepwise activation of oxidative metabolism during cell differentiation that was characterized by peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)–dependent stimulation of mitochondrial biogenesis and function, with concomitant reduction of the glycolytic enzyme content. Conversely, when podocytes were cultured in high glucose (20 mM), stepwise oxidative phosphorylation biogenesis was aborted, and a glycolytic switch occurred, with consecutive lactic acidosis. Expression of the master regulators of oxidative metabolism transcription factor A mitochondrial, PGC-1α, AMPK, and serine–threonine liver kinase B1 was altered by high glucose, as well as their downstream signaling networks. Focused transcriptomics revealed that myocyte-specific enhancer factor 2C (MEF2C) and myogenic factor 5 (MYF5) expression was inhibited by high glucose levels, and endoribonuclease-prepared small interfering RNA–mediated combined inhibition of those transcription factors phenocopied the glycolytic shift that was observed in high glucose conditions. Accordingly, a reduced expression of MEF2C, MYF5, and PGC-1α was found in kidney tissue sections that were obtained from patients with diabetic nephropathy. These findings obtained in human samples demonstrate that MEF2C-MYF5–dependent bioenergetic dedifferentiation occurs in podocytes that are confronted with a high-glucose milieu.—Imasawa, T., Obre, E., Bellance, N., Lavie, J., Imasawa, T., Rigothier, C., Delmas, Y., Combe, C., Lacombe, D., Benard, G., Claverol, S., Bonneu, M., Rossignol, R. High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy.

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“…This study shows the beneficial effects of UPS on heart failure. The dysfunction in the UPS system in RVF is confirmed by another study by Fessart et al [32]. The authors used rat models of RVF and performed proteomic profiling of the right ventricle.…”

Section: Ubiquitin Proteasesmentioning

confidence: 71%

Resuscitation of a dead cardiomyocyte

2015

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Although cardiac resuscitation can revive the whole body, the mechanisms are unclear. To this end, we propose that reviving a dead/dysfunctional cardiomyocyte will shed light on resuscitation mechanisms and pave the way to treat cardiac myopathies. The degradation of the myocyte cytoskeleton by the proteasome system which involves calpains, ubiquitin, caspases and matrix metalloproteases is the main focus of this review. The activation of calpains beyond the calpastatin-mediated inhibition due to extensive calcium harbor can lead to titin degradation, damage to the sarcomere and contractile dysfunction. The ubiquitin proteasome system can disturb the protein homeostasis within the cell and generate a dysfunctional myocyte. The matrix metalloproteases disrupt the collagen/elastin ratio and connexins to generate arrhythmias. The concept of cardiac resuscitation stems from protecting the myocyte cytoskeleton and keeping the protein homeostasis intact through management of the degradation machinery. In this regard, proteasome inhibitors for the degradation machinery have an elegant space. Recently exosomes have been identified potentially, as carriers of microRNAs or proteins that can modify the target cells. Exosomes loaded with the inhibitor "cargo" which comprises microRNAs, siRNAs or proteins to inhibit the degradation machinery can be a method of choice for cardiac resuscitation-a process difficult to execute.

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Proteomic remodeling of proteasome in right heart failure

Cited by 22 publications

References 56 publications

Animal model of reversible, right ventricular failure

Animal model of reversible, right ventricular failure

High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy

Resuscitation of a dead cardiomyocyte

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