Circadian oscillation in rat liver tryptophan pyrrolase and its analysis by substrate and hormone induction.
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Biomedical subjects
Publications and source records attributed to L Rensing.
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It is well known that hyperthermia causes a transient tolerance of cells to a second heat challenge (acquired thermotolerance). The present study addresses the question of whether hyperthermic pre-treatment also increases the tolerance against heat- and hydrogen peroxide-induced apoptosis in rat IPC-81 leukaemia cells. This cell line exhibits an aberrant heat shock response which is characterized by a lack of the inducible Hsp70 isoform, even under conditions of heat or hydrogen peroxide stress, while the constitutively expressed Hsc70 and the inducible isoform of hemoxygenase (HO-1) are strongly enhanced by heat stress (43.5 degrees C; 30 min). In spite of this Hsp70 deficiency, hyperthermic pre-treatment protects IPC-81 leukaemia cells against apoptotic cell death induced by heat or hydrogen peroxide, but is less effective against necrosis induced by higher doses of the applied stressors. Addition of hydrogen peroxide (25 microM) enhances the amount of bax mRNA, while the level of bcl-2 mRNA remains unchanged. No increase of bax mRNA, in contrast, could be detected in heat shock-primed IPC-81 cells when treated with hydrogen peroxide after a 12h recovery. These results indicate that hyperthermic pre-treatment may exert its anti-apoptotic function not only by enhanced expression of constitutive as well as inducible HSPs but also by lowering the level of bax transcripts and thereby increasing the Bcl-2/Bax ratio.
Circadian rhythms and cell cycles are endogenous self-sustained oscillations. They differ in several characteristics of the rhythmicity such as temperature dependency, reaction to external stimuli and the impact of protein synthesis. In multicellular organisms, the cell cycle very often is entrained by a circadian rhythm as has been analyzed in rats and mice, in particular. The same seems to hold true in cell cultures: Yoshida-ascites hepatoma cells, human embryonic fibroblasts, rat liver and rat hepatoma cells show circadian changes in the percentage of cells in G1-, S- and G2 + M-phases. The different phases within the cell cycle were determined by applying impulse cytophotometric methods. Some hypothetical mechanisms of entrainment of the cell cycle by circadian rhythms are discussed. Possible entrancing signals (Zeitgebers) are membrane and transport functions, cyclic nucleotides, nuclear non-histone proteins and their phosphorylation, and RNA synthesis. The maxima of the circadian rhythms of most of these functions in rat liver can be arranged in a certain temporal sequence.
Within an organism the sequence of events and processes during development, maturation, and aging is determined by endogenous and exogenous factors. The endogenous factors consist of oscillatory as well as of unidirectional mechanisms. An individual temporal order ("Eigenzeit") is the result of coupling between various oscillators, interactions between oscillators, and unidirectional processes and of stochastic events. Age-dependent changes of the diurnal rhythms in man and mammals serve as an example for age-dependent changes of the individual temporal order. The parameter of the endogenous (= circadian) diurnal rhythms are changed during embryogenesis, postnatal development, adolescence and aging: amplitude and phase delay increase during development and decrease with age. A higher frequency (ultradian) component predominates in childhood and old age. From experiments with model oscillators, lesioned central clocks in the hypothalamus of mammals and with an arrhythmic mutant of Drosophila, it is concluded that the changes of the temporal order are due to changes in the coupling properties of circadian and higher frequency oscillators. This may be true for the coupling between exogenous periodicities ("Zeitgeber") and endogenous clocks, their mutual interaction and their coordinative function. At present, it is not known whether these changes have consequences for human well-being and health. This may be the case, however, as concluded from indirect evidence.