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  • Inorganic Chemistry  (3)
  • Acid-Base Equilibrium  (1)
  • C-FLIPL  (1)
  • CASPASE-8 ACTIVATION  (1)
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  • 1
    Keywords: INHIBITOR ; MODEL ; NF-KAPPA-B ; T-CELLS ; CASPASE-8 ACTIVATION ; CD95-induced apoptosis ; LONG FORM ; RECEPTOR-INDUCED APOPTOSIS ; FADD ; C-FLIPL
    Abstract: This study explores the dilemma in cellular signaling that triggering of CD95 (Fas/APO-1) in some situations results in cell death and in others leads to the activation of NF-kappaB. We established an integrated kinetic mathematical model for CD95-mediated apoptotic and NF-kappaB signaling. Systematic model reduction resulted in a surprisingly simple model well approximating experimentally observed dynamics. The model postulates a new link between c-FLIP(L) cleavage in the death-inducing signaling complex (DISC) and the NF-kappaB pathway. We validated experimentally that CD95 stimulation resulted in an interaction of p43-FLIP with the IKK complex followed by its activation. Furthermore, we showed that the apoptotic and NF-kappaB pathways diverge already at the DISC. Model and experimental analysis of DISC formation showed that a subtle balance of c-FLIP(L) and procaspase-8 determines life/death decisions in a nonlinear manner. We present an integrated model describing the complex dynamics of CD95-mediated apoptosis and NF-kappaB signaling.
    Type of Publication: Journal article published
    PubMed ID: 20212524
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  • 2
    ISSN: 0365-9496
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0365-9496
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1439-6327
    Keywords: Local Cerebral Blood Flow ; Acid-Base Equilibrium ; Middle Cerebral Artery Occlusion ; Local O2 Pressure ; Steal Phenomenon ; Vaso-active Substances ; Lokale Gehirndurchblutung ; Säure-Basen-Haushalt ; Verschluß ; der Arteria cerebri media ; Lokaler Sauerstoffdruck ; Steal-Phänomen ; Vasoaktive Substanzen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei narkotisierten Katzen und Schweinen wurde die Arteria cerebri media einer Hemisphäre für verschieden lange Zeiten unterbunden. Sowohl im corticalen Versorgungsbereich der unterbundenen Arterie als auch in normalen, corticalen Bereichen wurden gleichzeitig Sauerstoffdruck, lokale corticale Durchblutung, Kohlendioxyddruck und Wasserstoffionenkonzentration registriert. Der arterielle Blutdruck wurde in der thorakalen Aorta gemessen. Die Änderungen der Sauerstoffdruckwerte auf der Gehirnrinde ermöglichten bei Unterbindung der Arteria cerebri media die Abgrenzung der corticalen, minderversorgten Felder. Die Durchblutung sank in diesen Bereichen unterschiedlich stark ab. Im Zentrum der Versorgungsbezirke erreichte die Durchblutung den Nullwert. Die CO2-Drucke stiegen stark an, das corticale pH wurde im minderdurchbluteten Bereich erheblich erniedrigt. Der arterielle Blutdruck reagierte bei der Unterbindung nicht signifikant. Nach kurzdauernder Ligatur und Wiedereröffnung des Gefäßes kam es zu reaktiven Hyperämien, die jedoch nach längerer Unterbindung von über 30 min Dauer nicht mehr nachzuweisen waren. Mit der reaktiven Hyperämie war ein Sauerstoffdruckanstieg über den Ausgangswert verbunden. Das corticale pH stieg jedoch in der Regel nicht mehr über den Ausgangswert an. Intravenöse Injektionen von Noradrenalin oder Papaverin zeigten im Zentrum des Ischämiebezirks keine Reaktionen, in den Randbereichen waren im Vergleich zu normalen Gehirnanteilen die Durchblutungsänderungen und die damit verbundenen Verschiebungen der übrigen Meßwerte geringer. Nach länger dauernder Unterbindung und Wiedereröffnung des Gefäßes kam es in dessen Versorgungsbereich zu erheblichen qualitativen und quantitativen Abweichungen der Reaktionen im Vergleich zum gesunden Gewebe.
    Notes: Summary In 15 cats and 12 pigs anesthetized with Nembutal, the middle cerebral artery (m. c. a.) was transiently ligated. The ligations were extended between 5 and 40 min. In the disturbed and in normal cortical regions the following values were simultaneously recorded: local cerebral blood flow with heat clearance, local cortical oxygen pressure, carbon dioxide pressure and local cortical pH. Arterial blood pressure was recorded in the thoracic aorta. The pattern of the cortical PO2-values during occlusion of the m. c. a. was an indicator for the size of the disturbed region. It could be seen that the areas supplied by the m. c. a. were different in the two species and additionally showed interindividual variations. During occlusion of the artery the local cortical Pco2 increased to maximal values of more than 300 mm Hg, the extracellular pH decreased down to 6.35 in cats and 6.7 in pigs when recorded within the centre of disturbed areas. In the normal hemisphere PCO2 and pH remained unchanged during the open-skull experiments. Arterial blood pressure remained nearly unchanged during occlusion. When the ligation was released, the blood pressure decreased in cats (in the mean: 4 mm Hg) but remained constant in pigs. After release of the ligation a reactive hyperemia in the disturbed region was observed if the occlusion lasted a few min. After long lasting ligation the reactive hyperemia was missed. The PO2, however, increased above the initial values in both cases and cortical pH remained more acid after short and long lasting ligations. The actions of intravenously injected nor-epinephrine and papaverine were different in the various parts of the disturbed hemisphere. In the surrounding of the disturbed region flow, pH, Po2 and Pco2 changed in the same direction as in normal brain tissue. In the centre of the infarcted area no reaction was observed. Intravenous injection of papaverine after release of long lasting m. c. a.-occlusions caused the local cortical cerebral blood flow to decrease in the centre of the disturbed regions when papaverin was applied but flow increased in the normal undisturbed tissue.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    ISSN: 0365-9496
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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