Ca2+-Binding Proteins of the EF-Hand Superfamily: Diagnostic and Prognostic Biomarkers and Novel Therapeutic Targets

Heizmann, Claus W.

doi:10.1007/978-1-4939-9030-6_11

Cited by 34 publications

(17 citation statements)

References 297 publications

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“…In humans and other higher vertebrates, regulation of intracellular calcium is associated with homeostasis and is regulated by calcium-binding proteins. These proteins have clinical importance in inflammation, cancer, neurology, allergy, cardiomyopathy and immune response [62]. Nevertheless, calcium-binding proteins and their importance on homeostasis are least studied in fish.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of posterior kidney of brown trout, Salmo trutta, during proliferative kidney disease

et al. 2019

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BackgroundTetracapsuloides bryosalmonae is a myxozoan parasite which causes economically important and emerging proliferative kidney disease (PKD) in salmonids. Brown trout, Salmo trutta is a native fish species of Europe, which acts as asymptomatic carriers for T. bryosalmonae. There is only limited information on the molecular mechanism involved in the kidney of brown trout during T. bryosalmonae development. We employed RNA sequencing (RNA-seq) to investigate the global transcriptome changes in the posterior kidney of brown trout during T. bryosalmonae development.MethodsBrown trout were exposed to the spores of T. bryosalmonae and posterior kidneys were collected from both exposed and unexposed control fish. cDNA libraries were prepared from the posterior kidney and sequenced. Bioinformatics analysis was performed using standard pipeline of quality control, reference mapping, differential expression analysis, gene ontology, and pathway analysis. Quantitative real time PCR was performed to validate the transcriptional regulation of differentially expressed genes, and their correlation with RNA-seq data was statistically analyzed.ResultsTranscriptome analysis identified 1169 differentially expressed genes in the posterior kidney of brown trout, out of which 864 genes (74%) were upregulated and 305 genes (26%) were downregulated. The upregulated genes were associated with the regulation of immune system process, vesicle-mediated transport, leucocyte activation, and transport, whereas the downregulated genes were associated with endopeptidase regulatory activity, phosphatidylcholine biosynthetic process, connective tissue development, and collagen catabolic process.ConclusionTo our knowledge, this is the first RNA-seq based transcriptome study performed in the posterior kidney of brown trout during active T. bryosalmonae development. Most of the upregulated genes were associated with the immune system process, whereas the downregulated genes were associated with other metabolic functions. The findings of this study provide insights on the immune responses mounted by the brown trout on the developing parasite, and the host molecular machineries modulated by the parasite for its successful multiplication and release.

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Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of posterior kidney of brown trout, Salmo trutta, during proliferative kidney disease

et al. 2019

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“…Fan et al demonstrated that patients showing ST-segment elevation myocardial infarction (STEMI) in the electrocardiogram (ECG) also had increased levels of S100A1 and that this S100 family member could complement current biomarkers [67]. It was also shown that S100A1 concentrations rise during early-stage acute myocardial ischemia, followed by a quick decrease, and thereby S100A1 could represent an early biomarker [68]. In addition, studies with S100A1 gene therapy in animal models predict a promising new strategy for the treatment of heart failure [69].…”

Section: Clinical Relevance Of S100 Proteinsmentioning

confidence: 99%

Friend or Foe: S100 Proteins in Cancer

Allgöwer

Kretz

Karstedt

et al. 2020

Cancers

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S100 proteins are widely expressed small molecular EF-hand calcium-binding proteins of vertebrates, which are involved in numerous cellular processes, such as Ca2+ homeostasis, proliferation, apoptosis, differentiation, and inflammation. Although the complex network of S100 signalling is by far not fully deciphered, several S100 family members could be linked to a variety of diseases, such as inflammatory disorders, neurological diseases, and also cancer. The research of the past decades revealed that S100 proteins play a crucial role in the development and progression of many cancer types, such as breast cancer, lung cancer, and melanoma. Hence, S100 family members have also been shown to be promising diagnostic markers and possible novel targets for therapy. However, the current knowledge of S100 proteins is limited and more attention to this unique group of proteins is needed. Therefore, this review article summarises S100 proteins and their relation in different cancer types, while also providing an overview of novel therapeutic strategies for targeting S100 proteins for cancer treatment.

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“…The small protein S100A4 belongs to the S100 family of EF-hand Ca 2+ -binding proteins, which, upon alterations in intracellular Ca 2+ concentration, change their conformation and their interaction with target proteins, modulating their activity [1]. S100A4 can control different intracellular pathways leading to a range of effects that are often cell- and tissue-type dependent [2].…”

Section: Introductionmentioning

confidence: 99%

The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis

Serrano

Apolloni

Rossi

et al. 2019

Cells

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S100A4, belonging to a large multifunctional S100 protein family, is a Ca2+-binding protein with a significant role in stimulating the motility of cancer and immune cells, as well as in promoting pro-inflammatory properties in different cell types. In the CNS, there is limited information concerning S100A4 presence and function. In this study, we analyzed the expression of S100A4 and the effect of the S100A4 transcriptional inhibitor niclosamide in murine activated primary microglia. We found that S100A4 was strongly up-regulated in reactive microglia and that niclosamide prevented NADPH oxidase 2, mTOR (mammalian target of rapamycin), and NF-κB (nuclear factor-kappa B) increase, cytoskeletal rearrangements, migration, and phagocytosis. Furthermore, we found that S100A4 was significantly up-regulated in astrocytes and microglia in the spinal cord of a transgenic rat SOD1-G93A model of amyotrophic lateral sclerosis. Finally, we demonstrated the increased expression of S100A4 also in fibroblasts derived from amyotrophic lateral sclerosis (ALS) patients carrying SOD1 pathogenic variants. These results ascribe S100A4 as a marker of microglial reactivity, suggesting the contribution of S100A4-regulated pathways to neuroinflammation, and identify niclosamide as a possible drug in the control and attenuation of reactive phenotypes of microglia, thus opening the way to further investigation for a new application in neurodegenerative conditions.

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Ca2+-Binding Proteins of the EF-Hand Superfamily: Diagnostic and Prognostic Biomarkers and Novel Therapeutic Targets

Cited by 34 publications

References 297 publications

Transcriptome profiling of posterior kidney of brown trout, Salmo trutta, during proliferative kidney disease

Transcriptome profiling of posterior kidney of brown trout, Salmo trutta, during proliferative kidney disease

Friend or Foe: S100 Proteins in Cancer

The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis

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