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Protein phosphorylation, caspase activation and PARP cleavage as time course related responses in Jurkat cells following different apoptotic stimuli
No full textProtein phosphorylation, caspase activation and PARP cleavage as time course related responses in Jurkat cells following different apoptotic stimuli
No full textHamster pancreatic beta cell lines with altered sensitivity towards apoptotic signalling by phosphatase inhibitors
No full text1 Specific inhibitors of serine/threonine phosphatases like okadaic acid can induce apoptotic cell death in the pancreatic beta cell line HIT. Cultivation in stepwise increased concentrations of okadaic acid enabled the isolation of HIT100R cells which proliferate at 100 nM okadaic acid (8 - 10 times the initially lethal concentration). 2 These two cell lines were used to characterize the events triggered by okadaic acid that led to apoptosis. Biochemical markers, e.g. cytochrome c release from mitochondria and increase of caspase-3-like activity, revealed that induction of apoptosis by 100 nM okadaic acid in parental HIT cells started with the release of cytochrome c. In HIT100R cells 500 nM okadaic acid were necessary to induce alterations comparable to those observed with 100 nM okadaic acid in non-resistant HIT cells. 3 In contrast to okadaic acid, the potency of the structurally different phosphatase inhibitor cantharidic acid to induce cytochrome c release, increase of caspase-3-like activity and DNA fragmentation was comparable in HIT and HIT100R cells. Thus, no cross-resistance between these phosphatase inhibitors seemed to exist. 4 Phosphatase activity in extracts from HIT and HIT100R cells did not differ in its total amount or in its sensitivity for okadaic acid. 5 Since higher concentrations of okadaic acid were needed to induce apoptosis in HIT100R cells, a compromised intracellular accumulation of the toxin appeared likely. Functional and structural analysis revealed that this was achieved by the development of the multidrug resistance phenotype in HIT100R cells. The underlying mechanism appeared to be the enhanced expression of the pgp1 but not the pgp2 gene
Selective reduction of amyloid beta 42 discriminates Alzheimer's disease from Huntington's disease: indication for distinct pathological events in amyloid beta peptide aggregation
No full textDifferences in the kinetics of cantharidic acid induced apoptosis seem to be unrelated to missing p53 function
No full textSelective prevention of nitrostyrene induced apoptotic cell death by the aminothiol WR 1065
No full textSelective prevention of nitrostyrene induced apoptotic cell death by the aminothiol WR 1065
No full textApoptosis by 6-O-palmitoyl-L-ascorbic acid coincides with JNK-phosphorylation and inhibition of Mg2+-dependent phosphatase activity
No full text6-O-Palmitoyl ascorbic acid (PAA) has recently been used as a substitute for ascorbic acid because of its greater potency as an antioxidant. In detailed concentration response studies distinct cytotoxic effects of PAA at concentrations exceeding 100 muM were reported. Here we examined and further characterized this cytotoxicity. While ascorbic acid was tolerated well up to millimolar concentrations, PAA revealed an LC50 between 125 and 150 muM in rat GH(3) tumor cells. Morphological and biochemical observations suggested the induction of apoptosis at concentrations exceeding 125 muM with a prominent activation of caspase 3 at 250 PM after 4 hr. A subsequent pronounced fragmentation of DNA (DNA-ladder) was detected after 6 hr and was further enhanced after 12 hr. The activation of caspases and the cleavage of its substrate PARP was preceded by a distinct increase in the phosphorylation of stress activated JNK-kinases. This observation suggested that the agent affected signal transduction mechanisms regulating protein phosphorylation at serine/threonine residues in the cell. No effect of PAA on protein phosphatase 2A (PP2A)-like activity was observed while magnesium-dependent protein phosphatase activity, presumably PP2C, was inhibited concentration-dependently up to 75% at the respective concentrations. Thus, the cytotoxic, pro-apoptotic effect of PAA might be related to the inhibition of PP2C and the activation of JNK. (C) 2003 Elsevier Inc. All rights reserved
Differences in the kinetics of cantharidic acid induced apoptosis seem to be unrelated to missing p53 function
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