ORCID Profile
0000-0003-3330-4898
Current Organisation
Universitat Rostock
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Publisher: Cold Spring Harbor Laboratory
Date: 24-09-2018
DOI: 10.1101/404525
Abstract: To explore the molecular processes underlying some biological theme of interest based on public data, gene lists are used herein as input for the construction of annotated pathway maps, employing Cytoscape apps, and then high-throughput (“omics”) gene expression data are overlaid onto these maps. Seeded with a published set of marker genes of the senescence-associated secretory phenotype and the genes of the cellular senescence KEGG pathway, a gene rotein interaction network and annotated clusters (a “pathway map”) of cellular senescence are derived. The map can be amended, by adding some application-specific genes, and overlaid with gene expression data describing cellular senescence of fibroblasts and with disease-related gene expression data associated with prostate and pancreatic cancer, and with ischemic stroke, allowing insights into the role of cellular senescence in disease. Some gene expression data are derived from the “Biomarker Benchmark repository”. The pathway map approach can be followed in principle for any biological theme of interest, fostering much-needed independence from the investigator-biased expert networks usually used for overlaying gene expression data.
Publisher: Impact Journals, LLC
Date: 24-03-2015
Abstract: Mutations of mitochondrial (mt)DNA cause a variety of human diseases and are implicated in premature aging syndromes. Here we investigated a single nucleotide exchange (leucine to methionine) at position nt4738 in the mitochondrial NADH dehydrogenase subunit 2 (Nd2) gene of the respiratory chain. Primary fibroblasts derived from the conplastic mouse strain C57BL/6J-mtALR/LTJ with mutant enzyme, possessed high enzyme activity and ATP production and low ROS production. Furthermore, Nd2-mutant fibroblasts expressed lower senescence markers. Transcriptome analysis revealed that the members of the p38MAPK pathway were significantly downregulated in Nd2-mutant mice. In agreement, inhibition of p38MAPK with SB203580 enhanced proliferation and reduced cytokine secretion in fibroblasts. In Nd2-mutant mouse skin, the amount of Ki67-positive cells was significantly higher than in control skin. The higher amount of Ki67-positive cells and the thicker epidermis in Nd2-mutant mice strongly supported the in vitro data. In conclusion, Nd2 is a mitochondrial gene, involved in age-related signaling pathways.
Location: No location found
Location: United Kingdom of Great Britain and Northern Ireland
Location: Germany
No related grants have been discovered for Rüdiger Köhling.