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101.
102.
Zhang X Kurnasov OV Karthikeyan S Grishin NV Osterman AL Zhang H 《The Journal of biological chemistry》2003,278(15):13503-13511
Pyridine dinucleotides (NAD and NADP) are ubiquitous cofactors involved in hundreds of redox reactions essential for the energy transduction and metabolism in all living cells. In addition, NAD also serves as a substrate for ADP-ribosylation of a number of nuclear proteins, for silent information regulator 2 (Sir2)-like histone deacetylase that is involved in gene silencing regulation, and for cyclic ADP ribose (cADPR)-dependent Ca(2+) signaling. Pyridine nucleotide adenylyltransferase (PNAT) is an indispensable central enzyme in the NAD biosynthesis pathways catalyzing the condensation of pyridine mononucleotide (NMN or NaMN) with the AMP moiety of ATP to form NAD (or NaAD). Here we report the identification and structural characterization of a novel human PNAT (hsPNAT-3) that is located in the cytoplasm and mitochondria. Its subcellular localization and tissue distribution are distinct from the previously identified human nuclear PNAT-1 and PNAT-2. Detailed structural analysis of PNAT-3 in its apo form and in complex with its substrate(s) or product revealed the catalytic mechanism of the enzyme. The characterization of the cytosolic human PNAT-3 provided compelling evidence that the final steps of NAD biosynthesis pathways may exist in mammalian cytoplasm and mitochondria, potentially contributing to their NAD/NADP pool. 相似文献
103.
Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants 总被引:4,自引:0,他引:4
Dietary phenolic compounds are known to elicite vital cellular responses such as cell cycle arrest, apoptosis and differentiation by activating a cascade of molecular events. As there is an increasing interest to improve the efficacy of these compounds for use as potential chemopreventive agents, we wanted to understand the impact of phenolic compounds on target genes in prostate cancer. In this study we used human cDNA microarrays with 2400 clones consisting of 17 prosite motifs to characterize alterations in gene expression pattern in response to the phenolic antioxidants ellagic acid (EA) and resveratrol (RE). Over a 48-hr exposure of androgen - sensitive LNCaP cells to EA and RE, a total of 593 and 555 genes respectively, showed more than a two fold difference in expression. A distinct set of genes in both EA-and RE-treated cells may represent the signature profile of phenolic antioxidant-induced gene expression in LNCaP cells. Although extensive similarity was found between effects of EA - and RE - responsive genes in prostate cancer cells, out of 246 genes with overlapping responses, 25 genes showed an opposite effect. Quantitative RT-PCR was used to verify and validate the differential expression of selected genes identified from cDNA microarrays. In-depth analysis of the data from this study provided insight into the alterations in the p53 - responsive genes, p300, Apaf-1, NF-kBp50 and p65 and PPAR families of genes, suggesting the activation of multiple signaling pathways that leads to growth inhibition of LNCaP cells. This is a first study to look for changes in a large number of human genes in response to dietary compounds. 相似文献
104.
Narayanan K 《Indian journal of experimental biology》2002,40(7):842-845
Occurrence of an Entomopoxvirus (EPV) from a lepidopteran insect viz;. cotton bollworm, H. armigera (HaEPV) along with gross pathological symptoms is reported for the first time in India. Histopathological study revealed that the fat body being the most favoured site of infection followed by haemocytes and gut epithelium. HaEPV was found to be not cross infective to six of the agricultural lepidopteran insect pests except for the potato black cutworm, Agrotis segetum registering 100% mortality showing typical symptom. Further, safety of HaEPV was shown against beneficial insect like mulberry silkworm, Bombyx mori and an useful insect general predator, Chrysoperla carnea. 相似文献
105.
Lukin KA Yang CX Bellettini JR Narayanan BA 《Nucleosides, nucleotides & nucleic acids》2000,19(4):815-825
New diazabicycloundecenium and phosphazenium derivatives of purines are introduced for mild and efficient preparation of nucleoside analogs via in situ alkylation. Diazabicycloundecenium salts of purines were obtained directly as a result of an unusual reaction between two corresponding amino compounds. 相似文献
106.
We tested the hypothesis that the excitatory neurotransmitter receptor agonist, alpha amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), would worsen cerebral cortical oxygen supply/consumption balance during focal ischemia. In this study, we compared regional cerebral blood flow, arterial and venous O2 saturation, O2 extraction and oxygen consumption of ischemic and AMPA treated ischemic and control regions of rat brain. Ischemia was induced by middle cerebral artery (MCA) occlusion in isoflurane (1.4%) anesthetized Wistar rats. Twenty minutes after MCA occlusion, 10–5 M AMPA was applied to the ischemic cortex (IC) for a period of 40 min; the fluid was changed every 10 min. After 1 hr of ischemia, animals were sacrificed and regional cerebral blood flow (rCBF) was determined using the C14-iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen saturation were determined microspectrophotometrically. In control, the cerebral blood flow and oxygen consumption of the IC were significantly lower than the contralateral cortex (rCBF: 46 ± 20 vs. 81 ± 39 ml/min/100g, O2 consumption: 2.8 ± 1.4 vs. 3.6 ± 1.4 ml O2/min/100g). 10–5 M AMPA did not significantly alter regional cerebral blood flow and oxygen consumption of the IC, but did decrease the average venous O2 saturation of the IC from 50.2 ± 3.9% to 46.7 ± 1.6%. AMPA also significantly increased the frequency of small veins with less than 45% O2 saturation in the IC (8 out of 56 veins in IC vs. 18 out of 56 veins in AMPA treated IC). Thus, topical application of 10–5 M AMPA to the ischemic area worsens cerebral O2 balance and suggests that excitatory amino acids contribute to the degree of cerebral ischemia. 相似文献
107.
Christopher C. Pan Sanjay Kumar Nirav Shah Dale G. Hoyt Lukas J. A. C. Hawinkels Karthikeyan Mythreye Nam Y. Lee 《The Journal of biological chemistry》2014,289(37):25486-25496
Endoglin is a transforming growth factor β (TGF-β) co-receptor essential for angiogenesis and tumor vascularization. Endoglin modulates the crucial balance between pro- and anti-angiogenic signaling by activin receptor-like kinase (ALK) 1, 5, and TGF-β type II (TβRII) receptors. Despite its established role in physiology and disease, the mechanism of endoglin down-regulation remains unknown. Here we report that the conserved juxtamembrane cytoplasmic tyrosine motif (612YIY614) is a critical determinant of angiogenesis. Src directly phosphorylates this motif to induce endoglin internalization and degradation via the lysosome. We identified epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as Src-activators that induce endoglin turnover following 612YIY614 phosphorylation. Interestingly, Src phosphorylation of endoglin-612YIY614 was also an important process for receptor down-regulation by TRACON105 (TRC105), an endoglin-targeting antibody currently in clinical trials. The regulation of 612YIY614 phosphorylation was critical for angiogenesis, as both the phosphomimetic and unphosphorylatable mutants impaired endothelial functions including proliferation, migration, and capillary tube formation. Collectively, these findings establish Src and pro-angiogenic mitogens as critical mediators of endoglin stability and function. 相似文献
108.
Shalaka Mulherkar Feng Liu Qin Chen Anjana Narayanan Anthony D. Couvillon H. David Shine Kimberley F. Tolias 《PloS one》2013,8(6)
The assembly of neuronal circuits during development requires the precise navigation of axons, which is controlled by attractive and repulsive guidance cues. In the developing spinal cord, ephrinB3 functions as a short-range repulsive cue that prevents EphA4 receptor-expressing corticospinal tract and spinal interneuron axons from crossing the midline, ensuring proper formation of locomotor circuits. Here we report that the small GTPase RhoA, a key regulator of cytoskeletal dynamics, is also required for ephrinB3/EphA4-dependent locomotor circuit formation. Deletion of RhoA from neural progenitor cells results in mice that exhibit a rabbit-like hopping gait, which phenocopies mice lacking ephrinB3 or EphA4. Consistent with this locomotor defect, we found that corticospinal tract axons and spinal interneuron projections from RhoA-deficient mice aberrantly cross the spinal cord midline. Furthermore, we determined that loss of RhoA blocks ephrinB3-induced growth cone collapse of cortical axons and disrupts ephrinB3 expression at the spinal cord midline. Collectively, our results demonstrate that RhoA is essential for the ephrinB3/EphA4-dependent assembly of cortical and spinal motor circuits that control normal locomotor behavior. 相似文献
109.
H K Choi A Terzis R C Stevens R Bau R Haugwitz V L Narayanan M Wolpert-DeFilippes 《Biochemical and biophysical research communications》1988,156(3):1120-1124
Pt(IV)(dach)Cl4 (dach = cyclohexyldiamine) was reacted with guanosine and 9-methylguanine and their reaction products were analyzed by single-crystal x-ray diffraction. In both cases the resulting complexes, [Pt(dach)(guanosine)2]2+ and [Pt(dach)(9-methylguanine)2]2+ respectively, corresponded to an unanticipated reduction of the octahedral Pt(IV) starting material to a square planar Pt(II) species. The nature of the reducing agent is presently unknown. 相似文献
110.
Harini Narayanan Michael Sokolov Massimo Morbidelli Alessandro Butté 《Biotechnology and bioengineering》2019,116(10):2540-2549
Due to the lack of complete understanding of metabolic networks and reaction pathways, establishing a universal mechanistic model for mammalian cell culture processes remains a challenge. Contrarily, data-driven approaches for modeling these processes lack extrapolation capabilities. Hybrid modeling is a technique that exploits the synergy between the two modeling methods. Although mammalian cell cultures are among the most relevant processes in biotechnology and indeed looks ideal for hybrid modeling, their application has only been proposed but never developed in the literature. This study provides a quantitative assessment of the improvement brought by hybrid models with respect to the state-of-the-art statistical predictive models in the context of therapeutic protein production. This is illustrated using a dataset obtained from a 3.5 L fed-batch experiment. With the goal to robustly define the process design space, hybrid models reveal a superior capability to predict the time evolution of different process variables using only the initial and process conditions in comparison to the statistical models. Hybrid models not only feature more accurate prediction results but also demonstrate better robustness and extrapolation capabilities. For the future application, this study highlights the added value of hybrid modeling for model-based process optimization and design of experiments. 相似文献