Activation of KCNN3/SK3/K(Ca)2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia (613 views)
Glia (ISSN: 1098-1136), 2012 Dec; 60(12): 2050-2064.
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Paper type: Journal Article, Research Support, Non-U. S. Gov'T,
Impact factor: 5.466, 5-year impact factor: 5.374
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-84867647374&partnerID=40&md5=9c581ca4b2db5abcf27228d78a9eb699
Keywords: Animals, Newborn, Apamin Pharmacology, Calcium Signaling Drug Effects Physiology, Cells, Cultured, Cytokines Antagonists, Inhibitors Biosynthesis Physiology, Down-Regulation Drug Effects, Inflammation Mediators Antagonists, Inhibitors Physiology Toxicity, Lipopolysaccharides Antagonists, Inhibitors Toxicity, Inbred C57bl, Microglia Drug Effects Metabolism, Pyrazoles Antagonists, Pyrimidines Antagonists, Small-Conductance Calcium-Activated Potassium Channels Metabolism Physiology, Calcium Homeostasis, Cyppa, Potassium Kcnn Sk Kca2 Channels, Calcium Ion, Interleukin 6, N Cyclohexyl N [2 (3, 5 Dimethylpyrazol 1 Yl) 6 Methyl 4 Pyrimidinamine, Nitric Oxide, Potassium Channel Stimulating Agent, Pyrimidine Derivative, Small Conductance Calcium Activated Potassium Channel, Small Conductance Calcium Activated Potassium Channel 2 2, Tumor Necrosis Factor Alpha, Unclassified Drug, Animal Cell, Animal Tissue, Article, Calcium Cell Level, Calcium Transport, Cell Activation, Cell Proliferation, Controlled Study, Cytokine Production, Mouse, Nonhuman, Priority Journal,
Affiliations:
*** IBB - CNR ***
Institute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, 35032, Marburg, Germany. dolga@staff.uni-marburg.de
Department of Neurology, Philipps University of Marburg, 35043, Marburg, Germany
Institute of Biostructures and Bioimaging-CNR, 16-80131, Naples, Italy
Department of Medicine, University of California, Davis, CA, United States
References:
Not available.
Glia (ISSN: 1098-1136), 2012 Dec; 60(12): 2050-2064.
Export to BibTeX Export to EndNote
Paper type: Journal Article, Research Support, Non-U. S. Gov'T,
Impact factor: 5.466, 5-year impact factor: 5.374
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-84867647374&partnerID=40&md5=9c581ca4b2db5abcf27228d78a9eb699
Keywords: Animals, Newborn, Apamin Pharmacology, Calcium Signaling Drug Effects Physiology, Cells, Cultured, Cytokines Antagonists, Inhibitors Biosynthesis Physiology, Down-Regulation Drug Effects, Inflammation Mediators Antagonists, Inhibitors Physiology Toxicity, Lipopolysaccharides Antagonists, Inhibitors Toxicity, Inbred C57bl, Microglia Drug Effects Metabolism, Pyrazoles Antagonists, Pyrimidines Antagonists, Small-Conductance Calcium-Activated Potassium Channels Metabolism Physiology, Calcium Homeostasis, Cyppa, Potassium Kcnn Sk Kca2 Channels, Calcium Ion, Interleukin 6, N Cyclohexyl N [2 (3, 5 Dimethylpyrazol 1 Yl) 6 Methyl 4 Pyrimidinamine, Nitric Oxide, Potassium Channel Stimulating Agent, Pyrimidine Derivative, Small Conductance Calcium Activated Potassium Channel, Small Conductance Calcium Activated Potassium Channel 2 2, Tumor Necrosis Factor Alpha, Unclassified Drug, Animal Cell, Animal Tissue, Article, Calcium Cell Level, Calcium Transport, Cell Activation, Cell Proliferation, Controlled Study, Cytokine Production, Mouse, Nonhuman, Priority Journal,
Affiliations:
*** IBB - CNR ***
Institute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, 35032, Marburg, Germany. dolga@staff.uni-marburg.de
Department of Neurology, Philipps University of Marburg, 35043, Marburg, Germany
Institute of Biostructures and Bioimaging-CNR, 16-80131, Naples, Italy
Department of Medicine, University of California, Davis, CA, United States
References:
Not available.
Activation of KCNN3/SK3/K(Ca)2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia
In neurons, small-conductance calcium-activated potassium (KCNN/SK/KCa2) channels maintain calcium homeostasis after N-methyl-D-aspartate (NMDA) receptor activation, thereby preventing excitotoxic neuronal death. So far, little is known about the function of KCNN/SK/KCa2 channels in non-neuronal cells, such as microglial cells. In this study, we addressed the question whether KCNN/SK/KCa2 channels activation affected inflammatory responses of primary mouse microglial cells upon lipopolysaccharide (LPS) stimulation. We found that N-cyclohexyl-N- [2- (3, 5-dimethyl-pyrazol-1-yl) -6-methyl-4-pyrimidinamine (CyPPA), a positive pharmacological activator of KCNN/SK/KCa2 channels, significantly reduced LPS-stimulated activation of microglia in a concentration-dependent manner. The general KCNN/SK/KCa2 channel blocker apamin reverted these effects of CyPPA on microglial proliferation. Since calcium plays a central role in microglial activation, we further addressed whether KCNN/SK/KCa2 channel activation affected the changes of intracellular calcium levels, [Ca2+] i,, in microglial cells. Our data show that LPS-induced elevation of [Ca2+] i was attenuated following activation of KCNN2/3/KCa2. 2/KCa2. 3 channels by CyPPA. Furthermore, CyPPA reduced downstream events including tumor necrosis factor alpha and interleukin 6 cytokine production and nitric oxide release in activated microglia. Further, we applied specific peptide inhibitors of the KCNN/SK/KCa2 channel subtypes to identify which particular channel subtype mediated the observed anti-inflammatory effects. Only inhibitory peptides targeting KCNN3/SK3/KCa2. 3 channels, but not KCNN2/SK2/KCa2. 2 channel inhibition, reversed the CyPPA-effects on LPS-induced microglial proliferation. These findings revealed that KCNN3/SK3/KCa2. 3 channels can modulate the LPS-induced inflammatory responses in microglial cells. Thus, KCNN3/SK3/KCa2. 3 channels may serve as a therapeutic target for reducing microglial activity and related inflammatory responses in the central nervous system. 2012 Wiley Periodicals, Inc
In neurons, small-conductance calcium-activated potassium (KCNN/SK/KCa2) channels maintain calcium homeostasis after N-methyl-D-aspartate (NMDA) receptor activation, thereby preventing excitotoxic neuronal death. So far, little is known about the function of KCNN/SK/KCa2 channels in non-neuronal cells, such as microglial cells. In this study, we addressed the question whether KCNN/SK/KCa2 channels activation affected inflammatory responses of primary mouse microglial cells upon lipopolysaccharide (LPS) stimulation. We found that N-cyclohexyl-N- [2- (3, 5-dimethyl-pyrazol-1-yl) -6-methyl-4-pyrimidinamine (CyPPA), a positive pharmacological activator of KCNN/SK/KCa2 channels, significantly reduced LPS-stimulated activation of microglia in a concentration-dependent manner. The general KCNN/SK/KCa2 channel blocker apamin reverted these effects of CyPPA on microglial proliferation. Since calcium plays a central role in microglial activation, we further addressed whether KCNN/SK/KCa2 channel activation affected the changes of intracellular calcium levels, [Ca2+] i,, in microglial cells. Our data show that LPS-induced elevation of [Ca2+] i was attenuated following activation of KCNN2/3/KCa2. 2/KCa2. 3 channels by CyPPA. Furthermore, CyPPA reduced downstream events including tumor necrosis factor alpha and interleukin 6 cytokine production and nitric oxide release in activated microglia. Further, we applied specific peptide inhibitors of the KCNN/SK/KCa2 channel subtypes to identify which particular channel subtype mediated the observed anti-inflammatory effects. Only inhibitory peptides targeting KCNN3/SK3/KCa2. 3 channels, but not KCNN2/SK2/KCa2. 2 channel inhibition, reversed the CyPPA-effects on LPS-induced microglial proliferation. These findings revealed that KCNN3/SK3/KCa2. 3 channels can modulate the LPS-induced inflammatory responses in microglial cells. Thus, KCNN3/SK3/KCa2. 3 channels may serve as a therapeutic target for reducing microglial activity and related inflammatory responses in the central nervous system. 2012 Wiley Periodicals, Inc
Activation of KCNN3/SK3/K(Ca)2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia
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Activation of KCNN3/SK3/K(Ca)2. 3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia
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Ruggiero A, Marchant J, Squeglia F, Makarov V, De Simone A, Berisio R
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Impact Factor: 2.983
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Scalia M, Satriano C, Greca R, Stella AM, Rizzarelli E, Spina-Purrello V
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* Molecular determinants of inactivation of the resuscitation promoting factor B from Mycobacterium tuberculosis (678 views)
J Biomol Struct Dyn (ISSN: 0739-1102, 1538-0254electronic, 0739-1102linking), 2013 Feb 1; 31(2): 195-205.
Impact Factor: 2.983
View Export to BibTeX Export to EndNote
Scalia M, Satriano C, Greca R, Stella AM, Rizzarelli E, Spina-Purrello V
* PARP-1 inhibitors DPQ and PJ-34 negatively modulate proinflammatory commitment of human glioblastoma cells (672 views)
Neurochemical Research (ISSN: 1573-6903, 0364-3190), 2013 Jan; 38(1): 50-58.
Impact Factor: 2.551
View Export to BibTeX Export to EndNote
2 Records (2 excluding Abstracts).
Total impact factor: 5.534 (5.534 excluding Abstracts).
Total 5 year impact factor: 4.542 (4.542 excluding Abstracts).
Total impact factor: 5.534 (5.534 excluding Abstracts).
Total 5 year impact factor: 4.542 (4.542 excluding Abstracts).
613 views. Last view on Sunday 06 October 2024, 2:36:26
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