Expression of mortalin in patients with chronic atrial fibrillation

Kirmanoglou, Kiriakos; Hannekum, A; Schafler, A. E.

doi:10.1007/s00395-004-0477-4

Cited by 26 publications

(26 citation statements)

References 21 publications

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“…In the present study, however, we were able to detect robust functional patterns extending beyond this biological variability. The validity of our data-set is corroborated by expression patterns of a wide variety of genes known to be regulated in pmAF (including NPPB, 39 41 EDNRA, 42 EDNRB, 42 and mortalin 43 ). Still, many transcripts reported to be regulated in pmAF were not found to be differentially expressed between SR and pmAF in the present study (eg, different myosin isoforms 5 ).…”

Section: Limitation Of the Present Studymentioning

confidence: 63%

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

Barth¹,

Merk²,

Arnoldi³

et al. 2005

Circulation Research

189

172

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Abstract-Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether reexpression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression in patients with sinus rhythm and to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed downregulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile, and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent upregulation of transcripts involved in metabolic activities, suggesting an adaptive response to increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were 5 times more likely to be upregulated in atrial fibrillation (174 genes upregulated, 35 genes downregulated), whereas atrial-specific transcripts were predominantly downregulated (56 genes upregulated, 564 genes downregulated). Overall, in fibrillating atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be upregulated (eg, metabolic processes), whereas functional classes predominantly expressed in atrial myocardium were downregulated (eg, signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium. Key Words: atrial fibrillation Ⅲ gene expression Ⅲ atrial myocardium Ⅲ functional genomics A trial fibrillation (AF), the most common sustained arrhythmia, is associated with extensive structural, contractile, and electrophysiological remodeling, 1 stabilizing AF in the long run. Because current pharmacological treatment of AF is limited by ventricular proarrhythmia and inefficacy to prevent recurrences of AF, understanding the molecular events of these remodeling processes is essential for the development of new targeted therapeutic interventions. Even though knowledge of genes involved in remodeling processes exists on a gene-by-gene basis including transcripts of the extracellular matrix compartment, 2 ion channels, 1,3 and signal transduction molecules, 4 microarray analysis offers a broader and unbiased approach to identify pathophysiologically relevant pathways. Therefore, we performed a systematic functional analysis of gene expression in permanent atrial fibrillation (pmAF) based on information from the Gene Ontology (GO) database to relate expression changes of single transcripts to known remodeling processes.Moreover, atrial fibrillation has been shown to be associated with an atrial-to-ventricular switch by expr...

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Section: Limitation Of the Present Studymentioning

confidence: 63%

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

Barth¹,

Merk²,

Arnoldi³

et al. 2005

Circulation Research

189

172

View full text Add to dashboard Cite

show abstract

“…It has only been proven that combined and individual overexpression of chaperonins may protect cells from ischemia-reoxygenation induced cell death. It has also been shown that Hsp10/60 accumula- In the myocardium of patients with chronic atrial fibrillation, the expression of the mitochondrial heat shock proteins Hsp60 and Hsp10 is increased (Schafler et al 2002;Kirmanoglou et al 2004); similar to what happens in the brainstem after subarachnoid hemorrhage (Satoh et al 2003). It has been elucidated that myocyte protection by Hsp10 involves the mobile loop and attenuation of the Ras GTPase pathway (Lin et al 2004).…”

Section: Sat1mentioning

confidence: 94%

Heat shock protein 10 and signal transduction: a “capsula eburnea” of carcinogenesis?

Czarnecka

Campanella²,

Zummo³

et al. 2006

Cell Stress Chaper

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To date, little is known either about the physical interactions of heat shock protein 10 (Hsp10) with other proteins within the cell or its involvement in signal transduction pathways. Hsp10 has been considered mainly as a partner of Hsp60 in the Hsp60/10 protein folding machine. Only recently, Hsp10 was reported to interact with proteins involved in deoxyribonucleic acid checkpoint inactivation, termination of M-phase, messenger ribonucleic acid export, import of nuclear proteins, nucleocytoplasmic transport, and pheromone signaling pathways. At the same time, Hsp10 expression can be up-regulated in cancer cells, because it accumulates as the cell transformation progresses. Recent data suggest that Hsp10 may be not only a component of the folding machine but also an active player of the cell signaling network, influencing cell cycle, nucleocytoplasmic transport, and metabolism, with putative roles in the lack of cell differentiation and in the inhibition of apoptosis. In this review, we revise the involvement of Hsp10 in signal transduction pathways and its possible role in cancer etiology.

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“…53 In the myocardium of patients with chronic atrial fibrillation, the expression of the mitochondrial heat shock proteins HSP60 and HSP10 is increased, as well as in brain stem after subarachnoid haemorrhage. 54,55 It has been proposed that myocyte protection by Hsp10 involves the mobile loop and attenuation of the Ras GTP-ase pathway. 38 Hsp10 could also influence the function of signaling proteins, according to Shan et al 56 In this study, overexpression of Hsp10 was shown to increase the abundance of IGF-1R and IGF-1-stimulated receptor auto-phosphorylation, the number of functioning receptors and to amplify activation of IGF-1R signaling.…”

Section: Hsp10: When Small Is Not Always Beautifulmentioning

confidence: 99%

Mitochondrial chaperones in cancer: From molecular biology to clinical diagnostics

Czarnecka

Campanella²,

Zummo³

et al. 2006

Cancer Biology & Therapy

143

104

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Mitochondria are cell organelles involved in processes of cell life and death, and therefore also in tumoral transformation. Indeed, mitochondria dysfunction is a prominent feature of cancer cells. Mitochondrial proteins and DNA have also been previously studied as markers of tumorigenesis.Heat shock proteins (HSPs) are ubiquitous evolutionary conserved proteins. HSPs enhance their expression in stressed cells and they are involved in gene expression regulation, DNA replication, signal transduction, differentiation, apoptosis, cellular senescence or immortalization.This review reflects recent views on the role of some mitochondrial molecular chaperones as prohibitin, mortalin and HSP60/HSP10 complex and their modifications leading to cell transformation and cancer development. These molecules could represent modern molecular biomarkers for oncological management.

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Expression of mortalin in patients with chronic atrial fibrillation

Abstract: The increased expression of mortalin may represent an adaptive heat shock response to restore cellular homeostasis.

Cited by 26 publications

References 21 publications

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

Reprogramming of the Human Atrial Transcriptome in Permanent Atrial Fibrillation

Heat shock protein 10 and signal transduction: a “capsula eburnea” of carcinogenesis?

Mitochondrial chaperones in cancer: From molecular biology to clinical diagnostics

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