7 results on '"Culmsee, C"'
Search Results
2. NGF mediates the neuroprotective effect of the @b2-adrenoceptor agonist clenbuterol in vitro and in vivo: evidence from an NGF-antisense study
- Author
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Culmsee, C., Semkova, I., and Krieglstein, J.
- Published
- 1999
- Full Text
- View/download PDF
3. Small conductance Ca 2+ -activated K + channels in the plasma membrane, mitochondria and the ER: Pharmacology and implications in neuronal diseases.
- Author
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Honrath B, Krabbendam IE, Culmsee C, and Dolga AM
- Subjects
- Animals, Carbamates pharmacology, Carbamates therapeutic use, Cell Membrane drug effects, Endoplasmic Reticulum drug effects, Humans, Mitochondria drug effects, Nervous System Diseases drug therapy, Neurons drug effects, Neurons metabolism, Piperidines pharmacology, Piperidines therapeutic use, Potassium Channels, Calcium-Activated agonists, Potassium Channels, Calcium-Activated antagonists & inhibitors, Cell Membrane metabolism, Endoplasmic Reticulum metabolism, Mitochondria metabolism, Nervous System Diseases metabolism, Potassium Channels, Calcium-Activated metabolism
- Abstract
Ca
2+ -activated K+ (KCa ) channels regulate after-hyperpolarization in many types of neurons in the central and peripheral nervous system. Small conductance Ca2+ -activated K+ (KCa 2/SK) channels, a subfamily of KCa channels, are widely expressed in the nervous system, and in the cardiovascular system. Voltage-independent SK channels are activated by alterations in intracellular Ca2+ ([Ca2+ ]i ) which facilitates the opening of these channels through binding of Ca2+ to calmodulin that is constitutively bound to the SK2 C-terminus. In neurons, SK channels regulate synaptic plasticity and [Ca2+ ]i homeostasis, and a number of recent studies elaborated on the emerging neuroprotective potential of SK channel activation in conditions of excitotoxicity and cerebral ischemia, as well as endoplasmic reticulum (ER) stress and oxidative cell death. Recently, SK channels were discovered in the inner mitochondrial membrane and in the membrane of the endoplasmic reticulum which sheds new light on the underlying molecular mechanisms and pathways involved in SK channel-mediated protective effects. In this review, we will discuss the protective properties of pharmacological SK channel modulation with particular emphasis on intracellularly located SK channels as potential therapeutic targets in paradigms of neuronal dysfunction., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
4. SK channel activation modulates mitochondrial respiration and attenuates neuronal HT-22 cell damage induced by H2O2.
- Author
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Richter M, Nickel C, Apel L, Kaas A, Dodel R, Culmsee C, and Dolga AM
- Subjects
- Animals, Cell Death drug effects, Cell Line, Transformed, Electron Transport drug effects, Hippocampus cytology, Hippocampus metabolism, Mice, Mitochondria metabolism, Neurons metabolism, Oxidative Stress, Hippocampus drug effects, Hydrogen Peroxide pharmacology, Mitochondria drug effects, Neurons drug effects, Small-Conductance Calcium-Activated Potassium Channels metabolism
- Abstract
Previous studies established an essential role for small conductance calcium-activated potassium (SK) channels in neuronal cell death pathways induced by glutamate excitotoxicity in cortical neurons in vitro and after cerebral ischemia in vivo. In addition to the intracellular calcium deregulation, glutamate-induced cell death also involves mechanisms of oxidative stress and mitochondrial dysfunction. Therefore, we sought to investigate whether SK channel activation might also affect mechanisms of intrinsic death pathways induced by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). Exposure of immortalized hippocampal HT-22 cells to H2O2 imposed activation of a cascade of intracellular toxic events resulting in intracellular ROS production, mitochondrial loss of function, and ultimately cell death. Using a pharmacological approach to activate SK channels with CyPPA, we demonstrated a reduction of H2O2-mediated intracellular ROS production and cell death. Interestingly, CyPPA mediated neuroprotection in conditions of extracellular calcium and/or pyruvate depletion, pointing to a neuroprotective role of mitochondrial SK channels. Moreover, CyPPA partially inhibited H2O2-induced mitochondrial superoxide production, but did not prevent mitochondrial membrane depolarization. CyPPA treatment resulted in slight ATP depletion and a reduction of mitochondrial respiration/oxygen consumption. These findings postulate that SK channels mediate a protective effect by preventing neuronal death from subsequent oxidative stress through an adaptive metabolic response at the level of mitochondria. Therefore, SK channel activation may serve as a therapeutic target, where mitochondrial dysfunction and related mechanisms of oxidative stress contribute to progressive degeneration and death of neurons., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
5. Oxidative stress and neurodegeneration.
- Author
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White A, Culmsee C, and Beart P
- Subjects
- Humans, Neurodegenerative Diseases metabolism, Oxidative Stress
- Published
- 2013
- Full Text
- View/download PDF
6. Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons.
- Author
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Isele NB, Lee HS, Landshamer S, Straube A, Padovan CS, Plesnila N, and Culmsee C
- Subjects
- Animals, Bone Marrow Cells enzymology, Cells, Cultured, Culture Media, Conditioned, Enzyme Activation, Gerbillinae, Neurons enzymology, Rats, Rats, Sprague-Dawley, Bone Marrow Cells metabolism, Mitogen-Activated Protein Kinases metabolism, Neurons metabolism, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction, Stromal Cells cytology
- Abstract
Application of adult bone marrow stromal cells (BMSC) improves functional outcome in animal models of cerebral ischemia, traumatic brain injury, and spinal cord injury. Accumulating evidence suggests that such functional recovery after BMSC treatment is mediated by enhanced trophic support of the injured neurons and improved neuronal plasticity rather than tissue replacement by bone marrow-derived stem cells. Therefore, the aim of the present study was to explore the potential of non-hematopoietic BMSC to stimulate signaling pathways in neurons that mediate trophic effects and neuroprotection. In primary embryonic rat neurons, BMSC conditioned medium (CM) attenuated staurosporine (STS) or amyloid-beta peptide-induced apoptosis in a concentration-dependent manner. The neuroprotective effect of CM required several hours of pretreatment and was abolished by heating over 90 degrees C. Immunoblot analyses revealed that CM enhanced Erk1/2 and Akt phosphorylation in neurons, and the specific MEK1 inhibitor PD98059 or the phosphoinositide-3 kinase (PI3-K) inhibitor Ly294002 abolished the neuroprotective effect of CM. Further, double-conditioned medium (DCM) obtained from BMSC previously stimulated by medium from STS-challenged neurons showed a more potent anti-apoptotic effect compared to the single-conditioned medium. Overall, these findings demonstrate that BMSC trigger endogenous survival signaling pathways in neurons that mediate protection against apoptotic insults. Moreover, the interaction between stressed neurons and BMSC further amplifies the observed neuroprotective effect.
- Published
- 2007
- Full Text
- View/download PDF
7. The tyrosine phosphatase inhibitor orthovanadate mimics NGF-induced neuroprotective signaling in rat hippocampal neurons.
- Author
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Gerling N, Culmsee C, Klumpp S, and Krieglstein J
- Subjects
- Animals, Apoptosis drug effects, Cell Survival drug effects, Cells, Cultured, Enzyme Activation, Female, Hippocampus cytology, Immunoblotting, Immunohistochemistry, Microscopy, Fluorescence, Mitogen-Activated Protein Kinases metabolism, PC12 Cells, Phosphatidylinositol 3-Kinases metabolism, Pregnancy, Rats, Rats, Sprague-Dawley, Enzyme Inhibitors pharmacology, Hippocampus drug effects, Nerve Growth Factors pharmacology, Neurons drug effects, Neuroprotective Agents pharmacology, Protein Tyrosine Phosphatases antagonists & inhibitors, Signal Transduction drug effects, Vanadates pharmacology
- Abstract
Activation of the high affinity neurotrophin receptor tropomyosin-related kinase A (TrkA) by nerve growth factor (NGF) leads to phosphorylation of intracellular tyrosine residues of the receptor with subsequent activation of signaling pathways involved in neuronal survival such as the phosphoinositide-3-kinase (PI3-K)/protein kinase B (PKB/Akt) pathway and the mitogen-activated protein kinase (MAPK) cascade. In the present study, we tested whether inhibition of protein-tyrosine phosphatases (PTP) by orthovanadate could enhance tyrosine phosphorylation of TrkA thereby stimulating NGF-like survival signaling in embryonic hippocampal neurons. We found that the PTP inhibitor orthovanadate (1 microM) enhanced TrkA phosphorylation and protected neurons against staurosporine (STS)-induced apoptosis in a time-and concentration-dependent manner. Inhibition of PTP enhanced TrkA phosphorylation also in the presence of NGF antibodies indicating that NGF binding to TrkA was not required for the effects of orthovanadate. Moreover, orthovanadate enhanced phosphorylation of Akt and the MAPK Erk1/2 suggesting that the signaling pathways involved in the protective effect were similar to those activated by NGF. Accordingly, inhibition of PI3-K by wortmannin and MAPK-kinase (MEK) inhibition by UO126 abolished the neuroprotective effects. In conclusion, the results indicate that orthovanadate mimics the effect of NGF on survival signaling pathways in hippocampal neurons. Thus, PTP inhibition appears to be an appropriate strategy to trigger neuroprotective signaling pathways downstream of neurotrophin receptors.
- Published
- 2004
- Full Text
- View/download PDF
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