排序方式: 共有13条查询结果,搜索用时 640 毫秒
1.
Shriya Sahu Finly Philip Suzanne Scarlata 《The Journal of biological chemistry》2014,289(8):5134-5144
C3PO plays a key role in promoting RNA-induced gene silencing. C3PO consists of two subunits of the endonuclease translin-associated factor X (TRAX) and six subunits of the nucleotide-binding protein translin. We have found that TRAX binds strongly to phospholipase Cβ (PLCβ), which transmits G protein signals from many hormones and sensory inputs. The association between PLCβ and TRAX is thought to underlie the ability of PLCβ to reverse gene silencing by small interfering RNAs. However, this reversal only occurs for some genes (e.g. GAPDH and LDH) but not others (e.g. Hsp90 and cyclophilin A). To understand this specificity, we carried out studies using fluorescence-based methods. In cells, we find that PLCβ, TRAX, and their complexes are identically distributed through the cytosol suggesting that selectivity is not due to large scale sequestration of either the free or complexed proteins. Using purified proteins, we find that PLCβ binds ∼5-fold more weakly to translin than to TRAX but ∼2-fold more strongly to C3PO. PLCβ does not alter TRAX-translin assembly to C3PO, and brightness studies suggest one PLCβ binds to one C3PO octamer without a change in the number of TRAX/translin molecules suggesting that PLCβ binds to an external site. Functionally, we find that C3PO hydrolyzes siRNA(GAPDH) at a faster rate than siRNA(Hsp90). However, when PLCβ is bound to C3PO, the hydrolysis rate of siRNA(GAPDH) becomes comparable with siRNA(Hsp90). Our results show that the selectivity of PLCβ toward certain genes lies in the rate at which the RNA is hydrolyzed by C3PO. 相似文献
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Kelley R. Healey Santosh K. Katiyar Shriya Raj Thomas D. Edlind 《Molecular microbiology》2012,86(2):303-313
Infections with the azole‐refractory yeast Candida glabrata are now commonly treated with the echinocandins caspofungin (CSF) or micafungin (MCF). True resistance (> 32‐fold decreased susceptibility) to these lipopeptide inhibitors of cell wall synthesis is rare and strictly associated with mutations in integral membrane proteins Fks1 or Fks2. In contrast, mutants exhibiting 4‐ to 32‐fold CSF reduced susceptibility (CRS) were readily selected in vitro, and surprisingly demonstrated 4‐ to 32‐fold MCF increased susceptibility (MIS). Sequencing and gene deletion demonstrated that CRS–MIS is Fks‐independent. To explore alternative mechanisms, we initially employed Saccharomyces cerevisiae, and observed that CRS was conferred by multiple mutations (fen1Δ, sur4Δ, cka2Δ and tsc10‐ts) disrupting sphingolipid biosynthesis. Following this lead, C. glabrata fen1Δ and cka2Δ deletants were constructed, and shown to exhibit CRS–MIS. Sphingolipid analysis of CRS–MIS laboratory mutants and clinical isolates demonstrated elevated dihydrosphingosine (DHS) and phytosphingosine (PHS) levels, and consistent with this sequencing revealed fen1, sur4, ifa38 and sur2 mutations. Moreover, exogenous DHS or PHS conferred a CRS–MIS phenotype on wild‐type C. glabrata. Exogenous PHS failed, however, to suppress CRS–MIS in a sur2 mutant blocked in conversion of DHS to PHS, implying that accumulation of these intermediates confers CRS–MIS. We conclude that membrane sphingolipids modulate echinocandin–Fks interaction. 相似文献
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Prins PA Perati PR Kon V Guo Z Ramesh A Linton MF Fazio S Sampson UK 《Cellular physiology and biochemistry》2012,29(1-2):121-130
The objective of this study was to determine the effect of benzo[a]pyrene (BaP), an abundant environmental polycyclic aromatic hydrocarbon compound, on the pathogenesis of abdominal aortic aneurysms (AAA). Earlier studies have shown that BaP promotes vasculopathy, including atherosclerosis, a predisposing factor for AAA development. In two experimental arms, 203 apolipoprotein E knockout (ApoE-/-) mice were evaluated in 4 groups: BaP, angiotensin II (AngII), BaP+AngII and control. Mice in the first arm were exposed to 5mg/kg/week of BaP for 42 days, and in the second arm to 0.71mg/kg daily for 60 days. In arm one, AAA incidence was higher in the BaP+AngII (14/28) versus AngII (8/27) group (p < 0.05), rupture (n=3) was observed only in BaP+AngII treated mice (p < 0.05). In the second arm, AAA incidence did not differ between AngII (17/30) and BaP+AngII (16/29) groups. However, intact AAA diameter was larger in the BaP+AngII (2.3 ± 0.1mm) versus AngII (1.9 ± 0.1mm) group (p < 0.05), but AAA rupture did not differ (p=NS). In both experimental arms, BaP+AngII mice showed increased expression of tumor necrosis factor alpha (TNF-α), cyclophilin A (Cyp A), and matrix metalloproteinase-9 (MMP9) (p < 0.05). No AAA occurred in control or BaP groups. These findings suggest the role of BaP exposure in potentiating AAA pathogenesis, which may have potential public health significance. 相似文献
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Shriya Pant Apul Goel Pravin Kumar Gangwar Prashant Gupta Akancha Pandey Satya Narayan Sankhwar 《Bioinformation》2020,16(9):688
We explore the impact of CHIT1 gene mutation on clinical, biochemical parameters and response to outcome (remission/failure) of medical treatment in North Indian filarial chyluria (FC) patients. Data of 101 subjects of FC treated medically between March 2013 and April 2016 in whom CHIT1 gene polymorphism was determined were analyzed. Filarial etiology was confirmed by DEC-provocative test, immuno-chromatographic test and IgG/IgM-combo rapid antibody test. CHIT1 gene polymorphism was genotyped by polymerase chain reaction. Of 101 patients (mean age, 36.9±10.28 years; male: female, 3:1.2), 66 experienced remission (Group-A) while 35 experienced relapse or failed to respond (Group-B). A significant association was observed between CHIT1 genotypes and higher grade of disease (p= 0.001). Wild-type, heterozygous and homozygous mutant frequencies of CHIT1 genotypes were 78.6%, 72.5% and 27.8% in remission and 21.4%, 27.5% and 72.2%, in recurrence/failure, respectively. Our results showed that patients with mutant genotype (TT) of CHIT1 gene showed significantly higher rate of recurrence or failure to medical therapy than wild type (HH) genotypes [OR (95% CI) = 9.53 (1.84-49.21), p=0.011]. This preliminary study showed the impact of CHIT1 gene variants on treatment outcome in FC patients. This observation needs to be confirmed using studies with larger numbers of FC patients. 相似文献
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Shreyasi Dutta Shibojyoti Lahiri Amrita Banerjee Shriya Saha 《Journal of biomolecular structure & dynamics》2013,31(2):434-446
Mithramycin (MTR), an aureolic acid group of antitumor antibiotic is used for the treatment of several types of tumors. We have reported here the association of MTR with an essential micronutrient, manganese (Mn2+). Spectroscopic methods have been used to characterize and understand the kinetics and mechanism of complex formation between them. MTR forms a single type of complex with Mn2+ in the mole ratio of 2:1 [MTR: Mn2+] via a two step kinetic process. Circular dichroism (CD) spectroscopic study indicates that the complex [(MTR)2 Mn2+] has a right-handed twist conformation similar in structure with the complexes reported for Mg2+ and Zn2+. This conformation allows binding via minor groove of DNA with (G, C) base preference during the interaction with double-stranded B-DNA. Using absorbance, fluorescence, and CD spectroscopy we have shown that [(MTR)2 Mn2+] complex binds to double-stranded DNA with an apparent dissociation constant of 32?μM and binding site size of 0.2 (drug/nucleotide). It binds to chicken liver chromatin with apparent dissociation constant value 298?μM. Presence of histone proteins in chromatin inhibits the accessibility of the complex for chromosomal DNA. We have also shown that MTR binds to Mn2+ containing metalloenzyme manganese superoxide dismutase from Escherichia coli. 相似文献
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Asmin Tulpule Juan Guan Dana S. Neel Hannah R. Allegakoen Yone Phar Lin David Brown Yu-Ting Chou Ann Heslin Nilanjana Chatterjee Shriya Perati Shruti Menon Tan A. Nguyen Jayanta Debnath Alejandro D. Ramirez Xiaoyu Shi Bin Yang Siyu Feng Suraj Makhija Trever G. Bivona 《Cell》2021,184(10):2649-2664.e18
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Pravin Kumar Gangwar Satya Narayan Sankhwar Shriya Pant Bhupendra Pal Singh Abbas Ali Mahdi Rajender Singh 《Bioinformation》2021,17(8):715
We analysed the polymorphisms at rs78202224 (C/A) for HSF1 gene, rs139496713 (C/T) and rs45504694 (C/A) for HSF2 gene and rs116868327 (G/A) for UBE2I gene in 547 infertile cases (non-obstructive azoospermia = 464, asthenozoospermia = 83) and 419 proven fertile controls of similar age group and ethnicity. SNP genotyping was done using AgenaMassARRY platform (Agena Bioscience, CA). Common, heterozygous, rare genotypes and allelic frequencies were analysed using dominant, recessive and co-dominant models. Data shows no significant association between HSF1, HSF2 polymorphisms and male infertility. However, under dominant (GG vs GA+AA) and co-dominanat (GG vs GA) model, polymorphism at the rs116868327 (G/A) locus in UBE2I gene was found to be linked with asthenozoospermia in males with a significant odd-ratio of 6.91 (confidence interval at 95% was 1.52-31.46; p=0.017). Moreover, frequency of rare allele was higher (2.4%) compared to controls (0.4%). Thus, this data showed a significant risk of developing asthenozoospermic condition in males (Odds ratio= 6.75; Confidence interval at 95%= 1.50-30.49; P= 0.018]. Hence, more number of genotyping studies along with the functional assay in multiple cohorts is needed to validate potential variants associated with male infertility. 相似文献
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Petra A. Prins Michael F. Hill David Airey Sam Nwosu Prudhvidhar R. Perati Hagai Tavori MacRae F. Linton Valentina Kon Sergio Fazio Uchechukwu K. Sampson 《PloS one》2014,9(1)