Hsp90 and its co-chaperone, Sgt1, as autoantigens in dilated cardiomyopathy

Kapustian, L. M.; Vigontina, Olga A.; Rozhko, O. T.; Ryabenko, D. V.; Michowski, Wojciech; Leśniak, Wiesława; Filipek, Anna; Kroupskaya, I. V.; Sidorik, L. L.

doi:10.1007/s00380-011-0226-1

Cited by 13 publications

(8 citation statements)

References 31 publications

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“…As mentioned above, we have shown that Sgt1 interacts with Hsps (Hsp90 and Hsp70) through the C-terminal domain, which also binds S100A6, and that S100A6 competes for the binding [Nowotny et al, 2003;Spiechowicz et al, 2007] Our group has demonstrated that Sgt1 exhibits cochaperone properties and may also act as a chaperone itself since it is able to protect proteins from thermal aggregation as shown by the citrate synthase assay [Żabka et al, 2008]. Furthermore, we have shown for the first time that the level of Sgt1 increases due to stress conditions [Żabka et al, 2008;Kapustian et al, 2013] similarily to the level of Hsps. In the case of heat shock, the increase in Sgt1 level is caused by transcription stimulation of the Sgt1 gene by HSF-1 transcription factor that binds to the promoter.…”

Section: Involvement Of Sgt1 In Chaperone Complexes and Cell Prolifermentioning

confidence: 75%

Aktualny pogląd na komórkową funkcję S100A6 i jego ligandów, CacyBP/SIP i Sgt1

Filipek

2018

Postepy Biochem

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S100A6 jest białkiem wiążącym wapń, którego gen zidentyfikowano po raz pierwszy jako gen indukowany czynnikami wzrostu. Od tego czasu przyjmuje się, że S100A6 jest białkiem biorącym udział w proliferacji i pokrewnych procesach komórkowych. Podczas gdy struktura S100A6 i kinetyka wiązania Ca2+ zostały dość wcześnie określone to badania nad mechanizmem działania S100A6 są prowadzone stosunkowo od niedawna. Niemniej wydaje się oczywiste, że S100A6 pełni swoją funkcję w komórce poprzez oddziaływanie w wieloma ligandami, z których większość została zidentyfikowana w naszym zespole. Ostatnio nasze badania koncentrują się na dwóch ligandach S100A6, to jest białkach CacyBP/SIP i Sgt1, które posiadają też swoje własne białka docelowe. Długa lista ligandów S100A6, CacyBP/SIP i Sgt1 wskazuje, że białka te są składnikami złożonej sieci interakcji i mogą być zaangażowane nie tylko w proliferację ale również w wiele innych procesów komórkowych, z których różnicowanie czy odpowiedź na stres wydają się być najlepiej udokumentowane.

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Section: Involvement Of Sgt1 In Chaperone Complexes and Cell Prolifermentioning

confidence: 75%

Aktualny pogląd na komórkową funkcję S100A6 i jego ligandów, CacyBP/SIP i Sgt1

Filipek

2018

Postepy Biochem

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“…The complete list of compounds ranked by FPAScores is available in Additional file 8 . The compounds include promising drug candidates, for example, two heat shock protein 90 (HSP90) inhibitors are upregulated in dilated cardiomyopathy [ 16 ], and two PPAR inhibitors are regarded as pharmacological therapeutic targets [ 17 ]. Furthermore, overexpression of two Cyclin-dependent kinase 2 (CDK2) inhibitors results in smaller mononuclear cardiomyocytes [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

Principal component analysis-based unsupervised feature extraction applied to in silico drug discovery for posttraumatic stress disorder-mediated heart disease

2015

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BackgroundFeature extraction (FE) is difficult, particularly if there are more features than samples, as small sample numbers often result in biased outcomes or overfitting. Furthermore, multiple sample classes often complicate FE because evaluating performance, which is usual in supervised FE, is generally harder than the two-class problem. Developing sample classification independent unsupervised methods would solve many of these problems.ResultsTwo principal component analysis (PCA)-based FE, specifically, variational Bayes PCA (VBPCA) was extended to perform unsupervised FE, and together with conventional PCA (CPCA)-based unsupervised FE, were tested as sample classification independent unsupervised FE methods. VBPCA- and CPCA-based unsupervised FE both performed well when applied to simulated data, and a posttraumatic stress disorder (PTSD)-mediated heart disease data set that had multiple categorical class observations in mRNA/microRNA expression of stressed mouse heart. A critical set of PTSD miRNAs/mRNAs were identified that show aberrant expression between treatment and control samples, and significant, negative correlation with one another. Moreover, greater stability and biological feasibility than conventional supervised FE was also demonstrated. Based on the results obtained, in silico drug discovery was performed as translational validation of the methods.ConclusionsOur two proposed unsupervised FE methods (CPCA- and VBPCA-based) worked well on simulated data, and outperformed two conventional supervised FE methods on a real data set. Thus, these two methods have suggested equivalence for FE on categorical multiclass data sets, with potential translational utility for in silico drug discovery.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0574-4) contains supplementary material, which is available to authorized users.

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“…For example, hypoxia and tnF alpha synergistically induce heat shock protein 90 (Hsp90) [29] which prevents cell apoptosis via PI3-K/akt activation [30]. Hsp90 was reported to increase in DcM patients [31].…”

Section: Discussionmentioning

confidence: 99%

Exogenous midkine administration prevents cardiac remodeling in pacing-induced congestive heart failure of rabbits

et al. 2014

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Midkine (MK), a heparin-binding growth factor, has been shown to prevent cardiac remodeling after ischemic injury through its anti-apoptotic effect. Cell apoptosis is central to the pathophysiology of cardiac remodeling in congestive heart failure (CHF) of ischemic as well as non-ischemic origin. We hypothesized that MK exerts the anti-apoptotic cardioprotective effect in CHF of non-ischemic etiology. MK protein or vehicle (normal saline) was subcutaneously administered in tachycardia-induced CHF rabbits (right ventricular pacing, 350 beats/min, 4 weeks). The vehicle-treated rabbits (n = 19, control) demonstrated severe CHF and high mortality rate, whereas MK (n = 16) demonstrated a well-compensated state and a lower mortality rate. In echocardiography, left ventricular (LV) end-diastolic dimension decreased in MK versus control, whereas LV systolic function increased. In histological analysis (picrosirius red staining), MK decreased collagen deposition area compared with control. TUNEL staining showed that MK prevented cell apoptosis and minimized myocyte loss in the CHF rabbit ventricle, associated with activation of PI3-K/Akt signaling, producing a parallel decrease of Bax/Bcl-2 ratio. MK prevented progression of cardiac remodeling in the CHF rabbit, likely by activation of anti-apoptotic signaling. Exogenous MK application might be a novel therapeutic strategy for CHF due to non-ischemic origin.

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Hsp90 and its co-chaperone, Sgt1, as autoantigens in dilated cardiomyopathy

Cited by 13 publications

References 31 publications

Aktualny pogląd na komórkową funkcję S100A6 i jego ligandów, CacyBP/SIP i Sgt1

Aktualny pogląd na komórkową funkcję S100A6 i jego ligandów, CacyBP/SIP i Sgt1

Principal component analysis-based unsupervised feature extraction applied to in silico drug discovery for posttraumatic stress disorder-mediated heart disease

Exogenous midkine administration prevents cardiac remodeling in pacing-induced congestive heart failure of rabbits

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