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1.
Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus 总被引:1,自引:0,他引:1
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Ann M. Toth Patricia Devaux Roberto Cattaneo Charles E. Samuel 《Journal of virology》2009,83(2):961-968
The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKRkd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (Cko) virus but had no effect on the growth of either wild-type (WT) or V knockout (Vko) virus. Increased growth of the Cko virus in PKRkd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, Vko, or especially Cko virus caused significantly less apoptosis in PKRkd cells than in PKR-sufficient cells. Although apoptosis induced by Cko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of Cko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR. 相似文献
2.
Guangjie Li Futian Peng Lin Zhang Xingzheng Shi Zhaoyan Wang 《Molecular biology reports》2010,37(2):947-954
Sucrose non-fermenting-1-related protein kinase-1 (SnRK1) plays an important role in metabolic regulation in plant. To understand
the molecular mechanism of amino acids and carbohydrate metabolism in Malus hupehensis Rehd. var. pinyiensis Jiang (Pingyi Tiancha, PYTC), a full-length cDNA clone encoding homologue of SnRK1 was isolated from PYTC by Rapid Amplification
of cDNA Ends (RACE). The clone, designated as MhSnRK1, contains 2063 nucleotides with an open reading frame of 1548 nucleotides. The deduced 515 amino acids showed high identities
with other plant SnRK1 genes. Quantitative real-time PCR analysis revealed this gene was expressed in roots, stems and leaves. Exposing seedlings
to nitrate caused and initial decrease in expression of the MhSnRK1 gene in roots, leaves and stems in short term. Ectopic expression of MhSnRK1 in tomato mainly resulted in higher starch content in leaf and red-ripening fruit than wild-type plants. This result supports
the hypothesis that overexpression of SnRK1 causes the accumulation of starch in plant cells. All the results suggest that
MhSnRK1 may play important roles in carbohydrate and amino acid metabolisms. 相似文献
3.
Yunfan Sun Liang Wu Yu Zhong Kaiqian Zhou Yong Hou Zifei Wang Zefan Zhang Jiarui Xie Chunqing Wang Dandan Chen Yaling Huang Xiaochan Wei Yinghong Shi Zhikun Zhao Yuehua Li Ziwei Guo Qichao Yu Liqin Xu Jia Fan 《Cell》2021,184(2):404-421.e16
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4.
Ba(2+) current through the L-type Ca(2+) channel inactivates essentially by voltage-dependent mechanisms with fast and slow kinetics. Here we found that slow inactivation is mediated by an annular determinant composed of hydrophobic amino acids located near the cytoplasmic ends of transmembrane segments S6 of each repeat of the alpha(1C) subunit. We have determined the molecular requirements that completely obstruct slow inactivation. Critical interventions include simultaneous substitution of A752T in IIS6, V1165T in IIIS6, and I1475T in IVS6, each preventing in additive manner a considerable fraction of Ba(2+) current from inactivation. In addition, it requires the S405I mutation in segment IS6. The fractional inhibition of slow inactivation in tested mutants caused an acceleration of fast inactivation, suggesting that fast and slow inactivation mechanisms are linked. The channel lacking slow inactivation showed approximately 45% of the sustained Ba(2+) or Ca(2+) current with no indication of decay. The remaining fraction of the current was inactivated with a single-exponential decay (pi(f) approximately 10 ms), completely recovered from inactivation within 100 ms and did not exhibit Ca(2+)-dependent inactivation properties. No voltage-dependent characteristics were significantly changed, consistent with the C-type inactivation model suggesting constriction of the pore as the main mechanism possibly targeted by Ca(2+) sensors of inactivation. 相似文献
5.
Xiaozhong Huang Yujuan Shi Hongjin Chen Rongrong Le Xiaohua Gong Ke Xu Qihan Zhu Feixia Shen Zimiao Chen Xuemei Gu Xiaojun Chen Xiong Chen 《Cell death & disease》2020,11(12)
Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.Subject terms: Pharmacology, Molecular biology 相似文献
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Accumulation of the labdane diterpene Marrubiin in glandular trichome cells along the ontogeny of Marrubium vulgare plants 总被引:1,自引:0,他引:1
The content of the diterpene Marrubiin was assessed by GC-FID in leaves of Marrubium vulgare plants along their ontogeny. Maximum accumulation occurred just before flowering time and in fully expanded leaves. After
feeding the plants with radio labeled [3H]-geranyl geranyl diphosphate, up to 70% of the radioactivity was recovered in HPLC-Rt coincidental with authentic Marrubiin,
which was also characterized by GC-EIMS, thus confirming that the biosynthesis of Marrubiin proceeds through the 1-deoxy-D-xylulose-5-phosphate
pathway. The major accumulation of radioactivity occurred in glandular trichome cells, and the product remained stable throughout. 相似文献
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