The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Theo Wallimann - One of the best experts on this subject based on the ideXlab platform.
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hair bundles are specialized for atp delivery via Creatine Kinase
Neuron, 2007Co-Authors: Jungbum Shin, Theo Wallimann, Femke Streijger, Andy J Beynon, Theo A Peters, Laura Gadzala, Debra Mcmillen, Cory Bystrom, Peter G GillespieAbstract:Summary When stimulated strongly, a hair cell's mechanically sensitive hair bundle may consume ATP too rapidly for replenishment by diffusion. To provide a broad view of the bundle's protein complement, including those proteins participating in energy metabolism, we used shotgun mass spectrometry methods to identify proteins of purified chicken vestibular bundles. In addition to cytoskeletal proteins, proteins involved in Ca 2+ regulation, and stress-response proteins, many of the most abundant bundle proteins that were identified by mass spectrometry were involved in ATP synthesis. After β-actin, the cytosolic brain isoform of Creatine Kinase was the next most abundant bundle protein; at ∼0.5 mM, Creatine Kinase is capable of maintaining high ATP levels despite 1 mM/s ATP consumption by the plasma-membrane Ca 2+ -ATPase. Consistent with this critical role in hair bundle function, the Creatine Kinase circuit is essential for high-sensitivity hearing as demonstrated by hearing loss in Creatine Kinase knockout mice.
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Mitochondrial Creatine Kinase in human health and disease
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2006Co-Authors: Uwe Schlattner, Malgorzata Tokarska-schlattner, Theo WallimannAbstract:Mitochondrial Creatine Kinase (MtCK), together with cytosolic Creatine Kinase isoenzymes and the highly diffusible CK reaction product, phosphoCreatine, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. Mitochondrial proteolipid complexes containing MtCK form microcompartments that are involved in channeling energy in form of phosphoCreatine rather than ATP into the cytosol. Under situations of compromised cellular energy state, which are often linked to ischemia, oxidative stress and calcium overload, two characteristics of mitochondrial Creatine Kinase are particularly relevant: its exquisite susceptibility to oxidative modifications and the compensatory up-regulation of its gene expression, in some cases leading to accumulation of crystalline MtCK inclusion bodies in mitochondria that are the clinical hallmarks for mitochondrial cytopathies. Both of these events may either impair or reinforce, respectively, the functions of mitochondrial MtCK complexes in cellular energy supply and protection of mitochondria form the so-called permeability transition leading to apoptosis or necrosis.
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inhibition of the mitochondrial permeability transition by Creatine Kinase substrates requirement for microcompartmentation
Journal of Biological Chemistry, 2003Co-Authors: Max Dolder, Oliver Speer, Uwe Schlattner, Bernd Walzel, Theo WallimannAbstract:Abstract Mitochondria from transgenic mice, expressing enzymatically active mitochondrial Creatine Kinase in liver, were analyzed for opening of the permeability transition pore in the absence and presence of Creatine Kinase substrates but with no external adenine nucleotides added. In mitochondria from these transgenic mice, cyclosporin A-inhibited pore opening was delayed by Creatine or cycloCreatine but not by β-guanidinopropionic acid. This observation correlated with the ability of these substrates to stimulate state 3 respiration in the presence of extramitochondrial ATP. The dependence of transition pore opening on calcium and magnesium concentration was studied in the presence and absence of Creatine. If mitochondrial Creatine Kinase activity decreased (i.e. by omitting magnesium from the medium), protection of permeability transition pore opening by Creatine or cycloCreatine was no longer seen. Likewise, when Creatine Kinase was added externally to liver mitochondria from wild-type mice that do not express mitochondrial Creatine Kinase in liver, no protective effect on pore opening by Creatine and its analog was observed. All these findings indicate that mitochondrial Creatine Kinase activity located within the intermembrane and intercristae space, in conjunction with its tight functional coupling to oxidative phosphorylation, via the adenine nucleotide translocase, can modulate mitochondrial permeability transition in the presence of Creatine. These results are of relevance for the design of Creatine analogs for cell protection as potential adjuvant therapeutic tools against neurodegenerative diseases.
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Creatine Kinase and Creatine Transporter in Normal, Wounded, and Diseased Skin
Journal of Investigative Dermatology, 2002Co-Authors: Uwe Schlattner, Natalie Möckli, Oliver Speer, Sabine Werner, Theo WallimannAbstract:Skin comprises many cell types that are characterized by high biosynthetic activity and increased energy turnover. The Creatine Kinase system, consisting of Creatine Kinase isoenzymes and Creatine transporter, is known to be important to support the high energy demands in such cells. We analyzed the presence and the localization of these proteins in murine and human skin under healthy and pathologic conditions, using immunoblotting and confocal immunohistochemistry with our recently developed specific antibodies. In murine skin, we found high amounts of brain-type cytosolic Creatine Kinase coexpressed with lower amounts of ubiquitous mitochondrial Creatine Kinase, both mainly localized in suprabasal layers of the epidermis, different cell types of hair follicles, sebaceous glands, and the subcutaneous panniculus carnosus muscle. With exception of sebaceous glands, these cells were also expressing Creatine transporter. Muscle-type cytosolic Creatine Kinase and sarcomeric mitochondrial Creatine Kinase were restricted to panniculus carnosus. Immediately after wounding of murine skin, brain-type cytosolic Creatine Kinase and a Creatine transporter-subspecies were transiently upregulated about 3-fold as seen in immunoblots, whereas the amount of ubiquitous mitochondrial Creatine Kinase increased during days 10–15 after wounding. Healthy and psoriatic human skin showed a similar coexpression pattern of brain-type cytosolic Creatine Kinase, ubiquitous mitochondrial Creatine Kinase, and Creatine transporter in this pilot study, with Creatine transporter species being upregulated in psoriasis.
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the role of Creatine Kinase in inhibition of mitochondrial permeability transition
FEBS Letters, 1997Co-Authors: Eddie Ogorman, Giesela Beutner, Max Dolder, Alan P Koretsky, Dieter Brdiczka, Theo WallimannAbstract:Cyciosporin A sensitive swelling of mitochondria isolated from control mouse livers and from the livers of transgenic mice expressing human ubiquitous mitochondrial Creatine Kinase occurred in the presence of both 40 gM calcium and 5 gM atractyloside which was accompanied by a 2.5-fold increase over state 4 respiration rates. Creatine and cyclocrea- tine inhibited the latter only in transgenic liver mitochondria. Protein complexes isolated from detergent solubilised rat brain extracts, containing octameric mitochondrial Creatine Kinase, porin and the adenine nucleotide translocator, were reconstituted into malate loaded lipid vesicles. Dimerisation of Creatine Kinase in the complexes and exposure of the reconstituted complexes to 200 gM calcium induced a cyclosporin A sensitive malate release. No malate release occurred with complexes containing octameric Creatine Kinase under the same conditions. © 1997 Federation of European Biochemical Societies.
Max Dolder - One of the best experts on this subject based on the ideXlab platform.
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inhibition of the mitochondrial permeability transition by Creatine Kinase substrates requirement for microcompartmentation
Journal of Biological Chemistry, 2003Co-Authors: Max Dolder, Oliver Speer, Uwe Schlattner, Bernd Walzel, Theo WallimannAbstract:Abstract Mitochondria from transgenic mice, expressing enzymatically active mitochondrial Creatine Kinase in liver, were analyzed for opening of the permeability transition pore in the absence and presence of Creatine Kinase substrates but with no external adenine nucleotides added. In mitochondria from these transgenic mice, cyclosporin A-inhibited pore opening was delayed by Creatine or cycloCreatine but not by β-guanidinopropionic acid. This observation correlated with the ability of these substrates to stimulate state 3 respiration in the presence of extramitochondrial ATP. The dependence of transition pore opening on calcium and magnesium concentration was studied in the presence and absence of Creatine. If mitochondrial Creatine Kinase activity decreased (i.e. by omitting magnesium from the medium), protection of permeability transition pore opening by Creatine or cycloCreatine was no longer seen. Likewise, when Creatine Kinase was added externally to liver mitochondria from wild-type mice that do not express mitochondrial Creatine Kinase in liver, no protective effect on pore opening by Creatine and its analog was observed. All these findings indicate that mitochondrial Creatine Kinase activity located within the intermembrane and intercristae space, in conjunction with its tight functional coupling to oxidative phosphorylation, via the adenine nucleotide translocase, can modulate mitochondrial permeability transition in the presence of Creatine. These results are of relevance for the design of Creatine analogs for cell protection as potential adjuvant therapeutic tools against neurodegenerative diseases.
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the role of Creatine Kinase in inhibition of mitochondrial permeability transition
FEBS Letters, 1997Co-Authors: Eddie Ogorman, Giesela Beutner, Max Dolder, Alan P Koretsky, Dieter Brdiczka, Theo WallimannAbstract:Cyciosporin A sensitive swelling of mitochondria isolated from control mouse livers and from the livers of transgenic mice expressing human ubiquitous mitochondrial Creatine Kinase occurred in the presence of both 40 gM calcium and 5 gM atractyloside which was accompanied by a 2.5-fold increase over state 4 respiration rates. Creatine and cyclocrea- tine inhibited the latter only in transgenic liver mitochondria. Protein complexes isolated from detergent solubilised rat brain extracts, containing octameric mitochondrial Creatine Kinase, porin and the adenine nucleotide translocator, were reconstituted into malate loaded lipid vesicles. Dimerisation of Creatine Kinase in the complexes and exposure of the reconstituted complexes to 200 gM calcium induced a cyclosporin A sensitive malate release. No malate release occurred with complexes containing octameric Creatine Kinase under the same conditions. © 1997 Federation of European Biochemical Societies.
Eddie Ogorman - One of the best experts on this subject based on the ideXlab platform.
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the role of Creatine Kinase in inhibition of mitochondrial permeability transition
FEBS Letters, 1997Co-Authors: Eddie Ogorman, Giesela Beutner, Max Dolder, Alan P Koretsky, Dieter Brdiczka, Theo WallimannAbstract:Cyciosporin A sensitive swelling of mitochondria isolated from control mouse livers and from the livers of transgenic mice expressing human ubiquitous mitochondrial Creatine Kinase occurred in the presence of both 40 gM calcium and 5 gM atractyloside which was accompanied by a 2.5-fold increase over state 4 respiration rates. Creatine and cyclocrea- tine inhibited the latter only in transgenic liver mitochondria. Protein complexes isolated from detergent solubilised rat brain extracts, containing octameric mitochondrial Creatine Kinase, porin and the adenine nucleotide translocator, were reconstituted into malate loaded lipid vesicles. Dimerisation of Creatine Kinase in the complexes and exposure of the reconstituted complexes to 200 gM calcium induced a cyclosporin A sensitive malate release. No malate release occurred with complexes containing octameric Creatine Kinase under the same conditions. © 1997 Federation of European Biochemical Societies.
Uwe Schlattner - One of the best experts on this subject based on the ideXlab platform.
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Mitochondrial Creatine Kinase in human health and disease
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2006Co-Authors: Uwe Schlattner, Malgorzata Tokarska-schlattner, Theo WallimannAbstract:Mitochondrial Creatine Kinase (MtCK), together with cytosolic Creatine Kinase isoenzymes and the highly diffusible CK reaction product, phosphoCreatine, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. Mitochondrial proteolipid complexes containing MtCK form microcompartments that are involved in channeling energy in form of phosphoCreatine rather than ATP into the cytosol. Under situations of compromised cellular energy state, which are often linked to ischemia, oxidative stress and calcium overload, two characteristics of mitochondrial Creatine Kinase are particularly relevant: its exquisite susceptibility to oxidative modifications and the compensatory up-regulation of its gene expression, in some cases leading to accumulation of crystalline MtCK inclusion bodies in mitochondria that are the clinical hallmarks for mitochondrial cytopathies. Both of these events may either impair or reinforce, respectively, the functions of mitochondrial MtCK complexes in cellular energy supply and protection of mitochondria form the so-called permeability transition leading to apoptosis or necrosis.
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inhibition of the mitochondrial permeability transition by Creatine Kinase substrates requirement for microcompartmentation
Journal of Biological Chemistry, 2003Co-Authors: Max Dolder, Oliver Speer, Uwe Schlattner, Bernd Walzel, Theo WallimannAbstract:Abstract Mitochondria from transgenic mice, expressing enzymatically active mitochondrial Creatine Kinase in liver, were analyzed for opening of the permeability transition pore in the absence and presence of Creatine Kinase substrates but with no external adenine nucleotides added. In mitochondria from these transgenic mice, cyclosporin A-inhibited pore opening was delayed by Creatine or cycloCreatine but not by β-guanidinopropionic acid. This observation correlated with the ability of these substrates to stimulate state 3 respiration in the presence of extramitochondrial ATP. The dependence of transition pore opening on calcium and magnesium concentration was studied in the presence and absence of Creatine. If mitochondrial Creatine Kinase activity decreased (i.e. by omitting magnesium from the medium), protection of permeability transition pore opening by Creatine or cycloCreatine was no longer seen. Likewise, when Creatine Kinase was added externally to liver mitochondria from wild-type mice that do not express mitochondrial Creatine Kinase in liver, no protective effect on pore opening by Creatine and its analog was observed. All these findings indicate that mitochondrial Creatine Kinase activity located within the intermembrane and intercristae space, in conjunction with its tight functional coupling to oxidative phosphorylation, via the adenine nucleotide translocase, can modulate mitochondrial permeability transition in the presence of Creatine. These results are of relevance for the design of Creatine analogs for cell protection as potential adjuvant therapeutic tools against neurodegenerative diseases.
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Creatine Kinase and Creatine Transporter in Normal, Wounded, and Diseased Skin
Journal of Investigative Dermatology, 2002Co-Authors: Uwe Schlattner, Natalie Möckli, Oliver Speer, Sabine Werner, Theo WallimannAbstract:Skin comprises many cell types that are characterized by high biosynthetic activity and increased energy turnover. The Creatine Kinase system, consisting of Creatine Kinase isoenzymes and Creatine transporter, is known to be important to support the high energy demands in such cells. We analyzed the presence and the localization of these proteins in murine and human skin under healthy and pathologic conditions, using immunoblotting and confocal immunohistochemistry with our recently developed specific antibodies. In murine skin, we found high amounts of brain-type cytosolic Creatine Kinase coexpressed with lower amounts of ubiquitous mitochondrial Creatine Kinase, both mainly localized in suprabasal layers of the epidermis, different cell types of hair follicles, sebaceous glands, and the subcutaneous panniculus carnosus muscle. With exception of sebaceous glands, these cells were also expressing Creatine transporter. Muscle-type cytosolic Creatine Kinase and sarcomeric mitochondrial Creatine Kinase were restricted to panniculus carnosus. Immediately after wounding of murine skin, brain-type cytosolic Creatine Kinase and a Creatine transporter-subspecies were transiently upregulated about 3-fold as seen in immunoblots, whereas the amount of ubiquitous mitochondrial Creatine Kinase increased during days 10–15 after wounding. Healthy and psoriatic human skin showed a similar coexpression pattern of brain-type cytosolic Creatine Kinase, ubiquitous mitochondrial Creatine Kinase, and Creatine transporter in this pilot study, with Creatine transporter species being upregulated in psoriasis.
Dieter Brdiczka - One of the best experts on this subject based on the ideXlab platform.
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the role of Creatine Kinase in inhibition of mitochondrial permeability transition
FEBS Letters, 1997Co-Authors: Eddie Ogorman, Giesela Beutner, Max Dolder, Alan P Koretsky, Dieter Brdiczka, Theo WallimannAbstract:Cyciosporin A sensitive swelling of mitochondria isolated from control mouse livers and from the livers of transgenic mice expressing human ubiquitous mitochondrial Creatine Kinase occurred in the presence of both 40 gM calcium and 5 gM atractyloside which was accompanied by a 2.5-fold increase over state 4 respiration rates. Creatine and cyclocrea- tine inhibited the latter only in transgenic liver mitochondria. Protein complexes isolated from detergent solubilised rat brain extracts, containing octameric mitochondrial Creatine Kinase, porin and the adenine nucleotide translocator, were reconstituted into malate loaded lipid vesicles. Dimerisation of Creatine Kinase in the complexes and exposure of the reconstituted complexes to 200 gM calcium induced a cyclosporin A sensitive malate release. No malate release occurred with complexes containing octameric Creatine Kinase under the same conditions. © 1997 Federation of European Biochemical Societies.