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1.
G T Makoul D R Robinson A K Bhalla L H Glimcher 《Journal of immunology (Baltimore, Md. : 1950)》1985,134(4):2645-2650
To minimize complicating interactions inherent in heterogeneous cell populations, we used a panel of cloned murine autoreactive (E8.A1) and antigen-specific (HEL.C10, HEL.B14) T cell hybridomas to examine the effect of prostaglandin E2 (PGE2) on T cell activation. These T cells secrete interleukin 2 (IL 2) when co-cultured with a cloned population of I region-matched stimulator cells (TA3), or with mitogenic signals in the absence of TA3 stimulator cells. Physiologic concentrations of PGE2 inhibited the induction of IL 2 secretion by the T cell hybridomas tested, when they were activated either by TA3 cells or by mitogenic signals. IL 2 production was inhibited in a dose-dependent manner by concentrations of PGE2 between 10(-7) and 10(-11) M, with 50% inhibition occurring at 10(-10) M. Pretreatment of the T hybridoma cells with 10(-7) M PGE2 for 1 hr before culture also resulted in marked inhibition of IL 2 secretion. Similar pretreatment of the TA3 cells did not affect their ability to activate the T cell hybridomas. PGE2 at 10(-8) M induced a 30-fold increase in cAMP levels within 25 min of addition to culture of the E8.A1 T cell hybridoma, but caused no significant elevation of cAMP levels in TA3 cells. The direct addition of dibutyryl cAMP (dcAMP) to cultures of E8.A1 cells resulted in marked inhibition of IL 2 secretion when stimulated by TA3 or by mitogenic signals, with an average of 80% inhibition occurring at 10(-4) M dcAMP. PGE2 and dcAMP also inhibited the growth of E8.A1 cells. Initially, cell growth was virtually halted, but began to recover between 24 and 48 hr after the addition of either PGE2 or dcAMP. Neither PGE2 nor dcAMP inhibited the division of TA3 cells. High affinity binding sites for PGE2 were detected in the E8.A1 T cell hybridomas with an apparent Kd of 7.6 X 10(-10) M, which is consistent with the functional data. No specific binding was detected in the TA3 stimulator cells. These findings suggest that the immunosuppressive effects of PGE2 are localized to the T cell, are receptor regulated, and may be mediated by the associated increase of cAMP levels in the T cell hybridomas. 相似文献
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A. S. Khehra S. K. Bhalla 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1976,47(6):271-274
Summary The investigations were carried out with ten genetically diverse maize varieties and all possible crosses between them, including reciprocals, at two agro-climatically different locations in Punjab (India). The materials were studied in a split-split plot design with plant population level of 59200, 74000 and 98700 plants per hectare. The variances due to reciprocal cross effects were significant for plant height, ear height and ear girth in the pooled analysis and the effects were quite consistent over plant population levels and locations. The data on days to silk were recorded only at one location and highly significant reciprocal effects were observed. The cytoplasmic effects, however, did not depend on the cytoplasm alone but also on the interaction of genotype with cytoplasm. The reciprocal effects were more distinct in early × late combinations of varieties than in early × early or late × late combinations. Early parents when used as female tended to reduce plant and ear height and days to silk, indicating a common developmental pathway for these three traits. Since the cytoplasmic effects for these characters were not associated with significant effects on yield, the results can be of practical significance. The cytoplasmic effects for days to silk were maintained even in the F2 and back-crosses. These findings encourage the use of particular cytoplasm in developing early maturing varieties. 相似文献
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Chloroplast phosphoproteins: phosphorylation of a 12-kDa stromal protein by the redox-controlled kinase of thylakoid membranes 总被引:1,自引:0,他引:1
Activation of the redox-controlled protein kinase of thylakoid membranes is detectable in vivo by measuring radioisotope incorporation into the light-harvesting Chl a/b protein and four photosystem II proteins (8.3, 32, 34, and 44 kDa). In normal barley leaves, the kinase is active under both aerobic and anaerobic (N2) conditions, but in the Chl b-less chlorina f2 mutant it is active only under anaerobic conditions. The responsiveness of this enzyme in the mutant to changes in the gas phase has been exploited to distinguish its protein substrates from those of other leaf protein kinases. Most of the soluble phosphoproteins of normal and mutant leaves (including a conspicuously labeled 67-kDa polypeptide) are labeled equally under both aerobic and anaerobic conditions, indicating that they are not substrates of the redox-controlled protein kinase. The major exception is a 12-kDa phosphoprotein, which is labeled in the mutant only under anaerobic conditions. The 67- and 12-kDa phosphoproteins are located in the chloroplast and are labeled when isolated organelles are incubated with [32P]orthophosphate in the light. When thylakoids and stroma are prepared from chloroplasts and are incubated with [gamma-32P]ATP in vitro, the 12-kDa protein is phosphorylated in the thylakoid preparation and then released from the membranes into the medium. The electron transport inhibitor diuron blocks activation of the redox-controlled kinase and prevents phosphorylation of the 12-kDa protein, which is thus the first example of a soluble protein to be phosphorylated by the thylakoid-bound protein kinase. The 67-kDa protein is phosphorylated by a distinct stromal kinase whose activity is not sensitive to diuron. 相似文献
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Multiple transcription start sites and alternative splicing in the methylenetetrahydrofolate reductase gene result in two enzyme isoforms 总被引:4,自引:0,他引:4
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Yingrui Liu Brent A. Bell Ying Song Hye J. Kim Jacob K. Sterling Benjamin J. Kim Maura Poli Michelle Guo Kevin Zhang Aditya Rao Janet R. Sparrow Guanfang Su Joshua L. Dunaief 《Aging cell》2021,20(11)
Iron has been implicated in the pathogenesis of age‐related retinal diseases, including age‐related macular degeneration (AMD). Previous work showed that intravitreal (IVT) injection of iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features of the model: geographic atrophy and sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF in the photoreceptors, quantification of bisretinoids, and localization of carboxyethyl pyrrole, an oxidized adduct of docosahexaenoic acid associated with AMD. In mice given IVT ferric ammonium citrate (FAC), RPE died in patches that slowly expanded at their borders, like human geographic atrophy. There was green AF in the photoreceptor ellipsoid, a mitochondria‐rich region, 4 h after injection, followed later by gold AF in rod outer segments, RPE and subretinal myeloid cells. The green AF signature is consistent with flavin adenine dinucleotide, while measured increases in the bisretinoid all‐trans‐retinal dimer are consistent with the gold AF. FAC induced formation carboxyethyl pyrrole accumulation first in photoreceptors, then in RPE and myeloid cells. Quantitative PCR on neural retina and RPE indicated antioxidant upregulation and inflammation. Unexpectedly, reminiscent of sympathetic ophthalmia, autofluorescent myeloid cells containing abundant iron infiltrated the saline‐injected fellow eyes only if the contralateral eye had received IVT FAC. These findings provide mechanistic insights into the potential toxicity caused by AMD‐associated retinal iron accumulation. The mouse model will be useful for testing antioxidants, iron chelators, ferroptosis inhibitors, anti‐inflammatory medications, and choroidal neovascularization inhibitors. 相似文献