Stimulation of receptor-coupled phospholipase A2by interferon-γ
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The biomolecular mechanisms that mediate signal transduction by type II (gamma) interferon (IFN) are poorly understood. IFN-gamma is a potent growth inhibitory cytokine also endowed with antiviral, immunomodulatory, and differentiating activities on various cell targets, including neural cells. IFN-gamma induced a rapid and transient activation of phospholipase A2 in LAN-5, a human neuroblastoma cell line. A consequence of phospholipase A2 activation was the release of arachidonic acid and the generation of lysophospholipids from membrane phospholipids. Treatment of pre-labeled LAN-5 cells with a receptor-saturating concentration of IFN-gamma led to a time-dependent release of [3H]arachidonic acid into the culture media and generation of [32P]lysophosphatidylcholine. Pretreatment of cultures with the phospholipase A2 inhibitor, bromophenacyl bromide, markedly inhibited both [3H]arachidonic acid release and lysophosphatidylcholine production induced by IFN-gamma treatment. Pretreatment of LAN-5 cells with nordihydroguaiaretic acid, a lipoxygenase inhibitor, or with indomethacin, a cyclooxygenase inhibitor, amplified the release of [3H]arachidonic acid and production of lysophosphatidylcholine induced by non-saturating concentrations of IFN-gamma. In parallel, and with the same time-dependent effect, a significant decrease in phosphatidylcholine labeling was observed in IFN-gamma-treated cells, further indicating that a potential signal transduction mechanism of IFN-gamma is the hydrolysis of membrane phosphatidylcholine by phospholipase A2.Energy charge
Phosphomonoesters
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To obtain an in vitro method of LATS assay which is equally sensitive to a McKenzie bioassay, we compared the quality of cAMP generation-stimulation, thyroidal adenyl cyclase stimulation, and the stimulation of T3-release from mouse thyroid slices. Among those indicators of thyroid stimulation, stimulation by IgG of the release of T3 from incubated thyroid slices is the most sensitive, reproducible and reliable indicator, reflecting faithfully the results of a McKenzie bioassay. Stimulation of cAMP generation in slice manifested less sensitivity, but reasonable reproducibility. However, adenyl cyclase stimulation by IgG of patients with Graves' disease was erratic in two successive experiments, probably due to a non-specific effect of IgG. When adenyl cyclase stimulation was adopted as a sole indicator of thyroid stimulation, the results must be interpreted cautiously.
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Experiments were done on urethane anesthetized adult rabbits. Long-train electrical stimulation was delivered to the Bötzinger complex (Böt.C) to observe the changes in the peak amplitude of integrated phrenic nerve activity. Then, a long-train electrical stimulation was delivered to the locus coeruleus (LC) or monosodium glutamate was microinjected into the LC . Within a certain period of time, another long-train electrical stimulation was delivered to the Böt.C to observe the responses of phrenic nerve activity. We investigated whether the LC could modulate the inspiratory inhibition induced by electrical stimulation of the Böt.C. The results are as follows: (1) Within a certain period of time after a long-train electrical stimulation applied at the LC, the inspiratory inhibition produced by electrical stimulation at the Böt.C was significantly attenuated. Comparing with the control stimulation that was only delivered at Böt.C without pre-stimulation of the LC, the inspiratory inhibition was decreased by (28.78+/-19.49)%. (2) Similarly, after chemical stimulation of the LC with microinjection of monosodium glutamate, the inspiratory inhibition produced by electrical stimulation of Böt.C was also significantly attenuated [decreased by (19.18+/-8.06)%]. The results obtained suggest that the LC plays a role in the modulation of the inspiratory inhibition of Böt.C stimulation.
Locus coeruleus
Phrenic nerve
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The matured porcine oocytes were activated by ethanol stimulation and electrical stimulation.The results showed that the cleavage of electrical stimulation with two 1.6 kV/cm and 60 μs was higher(88.68%,94/106),and the cleavage rate of ethanol stimulation with 8% and 10 min was 84.21%(64/76).The method of electrical stimulation with two 1.6 kV/cm and 60 μs had higher cleavage rate,and laid the foundation for further study.
Parthenogenesis
Cleavage (geology)
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The ATP-gated P2X(4) receptor is a cation channel, which is important in various pathophysiological events. The architecture of the P2X(4) receptor in the activated state and how to change its structure in response to ATP binding are not fully understood. Here, we analyze the architecture and ATP-induced structural changes in P2X(4) receptors using fast-scanning atomic force microscopy (AFM). AFM images of the membrane-dissociated and membrane-inserted forms of P2X(4) receptors and a functional analysis revealed that P2X(4) receptors have an upward orientation on mica but lean to one side. Time-lapse imaging of the ATP-induced structural changes in P2X(4) receptors revealed two different forms of activated structures under 0 Ca(2+) conditions, namely a trimer structure and a pore dilation-like tripartite structure. A dye uptake measurement demonstrated that ATP-activated P2X(4) receptors display pore dilation in the absence of Ca(2+). With Ca(2+), the P2X(4) receptors exhibited only a disengaged trimer and no dye uptake was observed. Thus our data provide a new insight into ATP-induced structural changes in P2X(4) receptors that correlate with pore dynamics.
Trimer
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Objective To study the effects of uniform biaxial mechanical stimulation on cyclooxygenase (COX-2) expression in SD rat primary osteoblasts. Methods A new uniform biaxial mechanical stimulation model has been designed for the first time. The isolated rat primary osteoblasts were exposed to uniform biaxial mechanical stimulation at different intensities (20 000, 100 000 and 200 000 microstrains) for different time periods (2, 4 and 8 h). The expression changes of COX-2 protein caused by respective mechanical stimulation were detected by immunocytochemistry and Western blotting. Results The expression of COX-2 did not increase sigmificantly after mechanical stimulation for two hours, but was upregulated after four hour and eight hour stimulation, while in the control groups, nearly no COX-2 was expressed. In additon, the expression of COX-2 in four-hour stimulated group increased while in the eight-hour group decreased with mcreasing stimulation. Conclusion Uniform biaxial mechanical stimulation at a certain time period and intensity promotes the expression of COX-2 in rat primary osteoblasts.
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Electrical brain stimulation
Tegmentum
Brain stimulation reward
Brain stimulation
Lateral hypothalamus
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In the protocols of modern pharmacological studies of a self-stimulation reaction in rodents, stimulating electrodes are implanted as a rule unilaterally. The reinforcing properties of the left and right hypothalamus were suggested to be identical. The aim of the study was to clear up if the possibilities of the left and right hypothalamus to produce self-stimulation are similar or not. Methods. The study was carried out on adult male Wistar rats. The electrodes were implanted into the lateral hypothalamus bilaterally. The rats, in which an approach reaction was observed, learned self-stimulation in the Skinner box with stimulation of the left or right hypothalamus as a reinforcing agent descending thresholds of stimulation up to minimal one. Results. Self-stimulation of the left hypothalamus gave an approach reaction in the majority of rats (81.8%), self-stimulation reaction was developed in 72.7% of rats. Only 46.2% rats reacted on stimulation of the right hypothalamus, self-stimulation reaction was developed in 30.8% of rats. The thresholds of positive and negative reactions registered after electrical stimulation of both sides of hypothalamus were significantly differed (H(3, N = 31) = 14,92; p = 0,002). And these changes were not connected with lateralization but with sign of reaction: in general the thresholds of approach reaction were higher than thresholds of avoidance. Conclusion. In the paper, the fact of different possibility of approach reaction and self-stimulation development as a result of electrical stimulation of the left and right hypothalamus in rats has been described. After stimulation of the left hypothalamus, a possibility to receive positive reaction and to form self-stimulation on its basis is higher than after stimulation of the right hypothalamus. (For citation: Efimov NS, Bessolova YN, Karpova IV, et al. Asymmetry of reinforcing properties of the lateral hypothalamus in the self-stimulation test. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):37-41. doi: 10.17816/RCF16237-41).
Lateral hypothalamus
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Physical Stimulation
Sensory stimulation therapy
Stimulus (psychology)
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Ejaculation
Sexual stimulation
Lateral hypothalamus
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