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Start Over Author "Kressmann S" Topic apoptosis
2 results on '"Kressmann S"'

1. Age-related increase of oxidative stress-induced apoptosis in mice prevention by Ginkgo biloba extract (EGb761).

Author

Schindowski K, Leutner S, Kressmann S, Eckert A, and Müller WE

Subjects
Aging metabolism, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Alzheimer Disease physiopathology, Animals, Apoptosis physiology, Cell Nucleus drug effects, Cell Nucleus metabolism, Cell Nucleus ultrastructure, Cells, Cultured, Deoxyribose pharmacology, Female, Ginkgo biloba, Lymphocytes cytology, Lymphocytes metabolism, Mice, Mice, Inbred Strains, Models, Biological, Oxidative Stress physiology, Spleen cytology, Spleen drug effects, Spleen metabolism, Aging drug effects, Apoptosis drug effects, Free Radical Scavengers pharmacology, Lymphocytes drug effects, Oxidative Stress drug effects, Plant Extracts pharmacology, Reactive Oxygen Species metabolism
Abstract

Enhanced apoptosis and elevated levels of reactive oxygen species (ROS) play a major role in aging. In addition, several neurodegenerative diseases are associated with increased oxidative stress and apoptosis in neuronal tissue. Antioxidative treatment has neuro-protective effects. The aim of the present study was to evaluate changes of susceptibility to apoptotic cell death by oxidative stress in aging and its inhibition by the antioxidant Ginkgo biloba extract EGb761. We investigated basal and ROS-induced levels of apoptotic lymphocytes derived from the spleen in young (3 months) and old (24 months) mice. ROS were induced by 2-deoxy-D-ribose (dRib) that depletes the intracellular pool of reduced glutathione. Lymphocytes from aged mice accumulate apoptotic cells to a significantly higher extent under basal conditions compared to cells from young mice. Treatment with dRib enhanced this difference, implicating a higher sensitivity to ROS in aging. Apoptosis can be reduced in vitro by treatment with EGb761. In addition, mice were treated daily with 100 mg/kg EGb761 per os over a period of two weeks. ROS-induced apoptosis was significantly reduced in the EGb761 group. Interestingly, this effect seemed to be more pronounced in old mice.

Published
2001
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2. Pan-Raf co-operates with PI3K-dependent signalling and critically contributes to myeloma cell survival independently of mutated RAS

Author

Andreas Rosenwald, Kreßmann S, Manik Chatterjee, Andreas Brandl, Schraud H, Thorsten Stühmer, Claus-Jürgen Scholz, Andreas Beilhack, Ralf C. Bargou, Müller E, Daniela Brünnert, Anja Mottok, Bauer S, and Torsten Steinbrunn

Subjects
Proto-Oncogene Proteins B-raf, 0301 basic medicine, Cancer Research, Cell Survival, MAP Kinase Signaling System, Gene Expression, Apoptosis, Biology, Transcriptome, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, RNA interference, In vivo, Cell Line, Tumor, Humans, Phosphorylation, RNA, Small Interfering, Lenalidomide, Protein Kinase Inhibitors, Protein kinase B, PI3K/AKT/mTOR pathway, TOR Serine-Threonine Kinases, Hematology, Thalidomide, Cell biology, Enzyme Activation, Isoenzymes, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, Cell culture, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Mutation, ras Proteins, RNA Interference, Stem cell, Signal transduction, Multiple Myeloma, Protein Binding, Signal Transduction
Abstract

Direct therapeutic targeting of oncogenic RAS is currently still impossible due to lack of suitable pharmacological inhibitors. Because specific blockade of druggable RAS effectors might represent an alternative treatment approach, we evaluated the role of the Raf complex for multiple myeloma (MM) pathobiology. We found frequent overexpression of the Raf isoforms (A-, B- and C-Raf) and downstream activation of MEK1,2/ERK1,2 in MM cells. Concomitant inhibition of all Raf isoforms (pan-Raf inhibition) by RNAi or pharmacological inhibitors was required to strongly induce apoptosis in human MM cell lines (HMCLs), in primary MM cells in vitro, and in a syngeneic MM mouse model in vivo. The anti-MM effect of pan-Raf inhibition did not correlate with the RAS mutation status, and functionally appeared to involve both MEK-dependent and -independent mechanisms. Furthermore, transcriptome analyses revealed that pan-Raf activity affects PI3K-dependent signalling, thus highlighting a functional link between the RAS/Raf and PI3K/mTOR/Akt pro-survival pathways. Accordingly, pharmacological inhibition of PI3K strongly enhanced the anti-MM effect of pan-Raf inhibition in MM cell lines and in primary MM cells in vitro and in vivo. Concomitant pan-Raf/PI3K inhibition was also effective in carfilzomib- and lenalidomide-resistant MM models underscoring that this attractive therapeutic anti-MM strategy is suitable for immediate clinical translation.

Published
2016

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