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排序方式: 共有371条查询结果,搜索用时 15 毫秒
101.
Shumei Zhong Antonia Lucia Magnolo Meenakshi Sundaram Hu Zhou Erik F. Yao Enza Di Leo Paola Loria Shuai Wang Michelle Bamji-Mirza Lisheng Wang C. Jamie McKnight Daniel Figeys Yuwei Wang Patrizia Tarugi Zemin Yao 《The Journal of biological chemistry》2010,285(9):6453-6464
Five nontruncating missense APOB mutations, namely A31P, G275S, L324M, G912D, and G945S, were identified in heterozygous carriers of familial hypobetalipoproteinemia (FHBL) in the Italian population. To test that the FHBL phenotype was a result of impaired hepatic secretion of mutant apoB proteins, we performed transfection studies using McA-RH7777 cells stably expressing wild type or mutant forms of human apolipoprotein B-48 (apoB-48). All mutant proteins displayed varied impairment in secretion, with G912D the least affected and A31P barely secreted. Although some A31P was degraded by proteasomes, a significant proportion of it (although inappropriately glycosylated) escaped endoplasmic reticulum (ER) quality control and presented in the Golgi compartment. Degradation of the post-ER A31P was achieved by autophagy. Expression of A31P also decreased secretion of endogenous apoB and triglycerides, yet the impaired lipoprotein secretion did not lead to lipid accumulation in the cells or ER stress. Rather, expression of genes involved in lipogenesis was down-regulated, including liver X receptor α, sterol regulator element-binding protein 1c, fatty acid synthase, acetyl-CoA carboxylase 1, stearoyl-CoA desaturase 1, and lipin-1. These results suggest that feedback inhibition of hepatic lipogenesis in conjunction with post-ER degradation of misfolded apoB proteins can contribute to reduce fat accumulation in the FHBL liver. 相似文献
102.
103.
Meenakshi Sundaram Shumei Zhong Maroun Bou Khalil Philip H. Links Yang Zhao Jahangir Iqbal M. Mahmood Hussain Robin J. Parks Yuwei Wang Zemin Yao 《Journal of lipid research》2010,51(1):150-161
Apolipoprotein (apo) C-III plays a regulatory role in VLDL lipolysis and clearance. In this study, we determined a potential intracellular role of apoC-III in hepatic VLDL assembly and secretion. Stable expression of recombinant apoC-III in McA-RH7777 cells resulted in increased secretion efficiency of VLDL-associated triacylglycerol (TAG) and apoB-100 in a gene-dosage-dependent manner. The stimulatory effect of apoC-III on TAG secretion was manifested only when cells were cultured under lipid-rich (i.e., media supplemented with exogenous oleate) but not lipid-poor conditions. The stimulated TAG secretion was accompanied by increased secretion of apoB-100 and apoB-48 as VLDL1. Expression of apoC-III also increased mRNA and activity of microsomal triglyceride transfer protein (MTP). Pulse-chase experiments showed that apoC-III expression promoted VLDL1 secretion even under conditions where the MTP activity was inhibited immediately after the formation of lipid-poor apoB-100 particles, suggesting an involvement of apoC-III in the second-step VLDL assembly process. Consistent with this notion, the newly synthesized apoC-III was predominantly associated with TAG within the microsomal lumen that resembled lipid precursors of VLDL. Introducing an Ala23-to-Thr mutation into apoC-III, a naturally occurring mutation originally identified in two Mayan Indian subjects with hypotriglyceridemia, abolished the ability of apoC-III to stimulate VLDL secretion from transfected cells. Thus, expression of apoC-III in McA-RH7777 cells enhances hepatic TAG-rich VLDL assembly and secretion under lipid-rich conditions. 相似文献
104.
Gunjan D. Mehta Meenakshi P. Agarwal Santanu Kumar Ghosh 《Molecular genetics and genomics : MGG》2010,284(2):75-94
The centromere is a genetic locus, required for faithful chromosome segregation, where spindle fibers attach to the chromosome
through kinetochore. Loss of centromere or formation of multiple centromeres on a single chromosome leads to chromosome missegregation
or chromosome breakage, respectively, which are detrimental for fitness and survival of a cell. Therefore, understanding the
mechanism of centromere locus determination on the chromosome and perpetuation of such a locus in subsequent generation (known
as centromere identity) is very fundamental to combat conditions like aneuploidy, spontaneous abortion, developmental defects,
cell lethality and cancer. Recent studies have come up with different models to explain centromere identity. However, the
exact mechanism still remains elusive. It has been observed that most eukaryotic centromeres are determined epigenetically
rather than by a DNA sequence. The epigenetic marks that are instrumental in determining centromere identity are the histone
H3 variant, CENP-A and the specialized posttranslational modification of the core histones. Here we will review the recent
studies on the factors responsible for generating unique centromeric chromatin and how it perpetuates during cell division
giving the present-day models. We will further focus on the probable mechanism of de novo centromere formation with an example
of neocentromere. As a matter of similitude, this review will include marking extrachromosomal chromatin to be served as a
partitioning locus by deposition of CENP-A homolog in budding yeast. 相似文献
105.
Nagarajan R Upreti M 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2006,3(3):232-238
In this paper, correlation of the pixels comprising a microarray spot is investigated. Subsequently, correlation statistics, namely, Pearson correlation and Spearman rank correlation, are used to segment the foreground and background intensity of microarray spots. The performance of correlation-based segmentation is compared to clustering-based (PAM, k-means) and seeded-region growing techniques (SPOT). It is shown that correlation-based segmentation is useful in flagging poorly hybridized spots, thus minimizing false-positives. The present study also raises the intriguing question of whether a change in correlation can be an indicator of differential gene expression. 相似文献
106.
Meenakshi J Anupama Goswami SK Datta K 《Biochemical and biophysical research communications》2003,300(3):686-693
Hyaluronan binding protein 1 (HABP1) is a ubiquitously expressed multifunctional phospho-protein that interacts with a wide range of ligands and is implicated in cell signalling. Recently, we have reported that HABP1 is an endogenous substrate for MAP kinase and upon mitogenic stimulation it is translocated to the nucleus in a MAP kinase-dependent manner (Biochem. Biophys. Res. Commun. 291(4) (2002) 829-837). This prompted us to investigate the role of HABP1 in cell growth or otherwise in low MAP kinase background. We demonstrate that HABP1, when overexpressed in normal rat skin fibroblasts, remained in the cytosol, primarily concentrated around the nuclear periphery. However, HABP1 overexpressing cells showed extensive vacuolation and reduced growth rate, which was corrected by frequent medium replenishment. Further investigation revealed that HABP1 overexpressing cells undergo apoptosis, as detected by TUNEL assay, induction of Bax expression, and FACS analysis, and they failed to enter into the S-phase. Periodic medium supplementation prevented these cells from undergoing apoptotic death. We also demonstrate that upon induction of apoptosis in HeLa cells by cisplatin, HABP1 level is upregulated, indicating a correlation between HABP1 and cell death in a normal cellular environment. 相似文献
107.
Falcipain-2 (FP-2) is a dual-function protease that cleaves hemoglobin at the early trophozoite stage and erythrocyte membrane ankyrin and protein 4.1 at the late stages of parasite development. FP-2-mediated cleavage of ankyrin and protein 4.1 is postulated to cause membrane instability facilitating parasite release in vivo. To test this hypothesis, here we have determined the precise peptide sequence at the hydrolysis site of ankyrin to develop specific inhibitor(s) of FP-2. Mass spectrometric analysis of the hydrolysis products showed that FP-2-mediated cleavage of ankyrin occurred immediately after arginine 1,210. A 10-mer peptide (ankyrin peptide, AnkP) containing the cleavage site completely inhibited the FP-2 enzyme activity in vitro and abolished all of the known functions of FP-2. To determine the effect of this peptide on the growth and development of P. falciparum, the peptide was delivered into intact parasite-infected red blood cells (RBCs) via the Antennapedia homeoprotein internalization domain. Growth and maturation of trophozoites and schizonts was markedly inhibited in the presence of the fused AnkP peptide. <10% of new ring-stage parasites were detected compared with the control sample. Together, our results identify a specific peptide derived from the spectrin-binding domain of ankyrin that blocks late-stage malaria parasite development in RBCs. Confocal microscopy with FP-2-specific antibodies demonstrated the proximity of the enzyme in apposition with the RBC membrane, further corroborating the proposed function of FP-2 in the cleavage of RBC skeletal proteins. 相似文献
108.
Taj SA Gurumurthy P Suresh R Narayanan S Suman Meenakshi S Sanghvi YS 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):1327-1330
An efficient four step process for the preparation of 5'-O-(4,4'-dimethoxytrityl)-N2-isobutyryl-2'-O-(2-methoxyethyl)-guanosine 1 was developed. Direct 2'-O-alkylation of 2,6-diaminopurine riboside 2 was accomplished via inexpensive and commercially available reagents such as KOH, DMSO and alkyl halides at room temperature in 4-6 hrs. Pure 2'-O-(2-methoxyethyl)-DAPR 3 was isolated by crystallization from methanol. Enzymatic deamination of 3 followed by selective N2-isobutyrylation and 5'-O-dimethoxytritylation furnished desired 1 in high yield and purity. Fully optimized four step synthetic process has been scaled up to the pilot plant level. 相似文献
109.
8-quinolinamines and their pro prodrug conjugates as potent blood-schizontocidal antimalarial agents
Vangapandu S Sachdeva S Jain M Singh S Singh PP Kaul CL Jain R 《Bioorganic & medicinal chemistry》2003,11(21):4557-4568
Synthesis and antimalarial activities of N8-(4-amino-1-methylbutyl)-5-alkoxy-4-ethyl-6-methoxy-8-quinolinamines (5) and their pro prodrug analogues (6-7) prepared by covalently linking 5 to the redox-sensitive (8) and esterase-sensitive (9) linkers through the amide linkage are reported. The most effective 8-quinolinamines [5c (R=C5H11) and 5f (R=C8H17)] have exhibited in vitro and in vivo biological efficacy superior to that of the standard drug chloroquine against both drug-sensitive and drug-resistant malaria strains. Analogues 6-7 were evaluated for in vivo blood-schizontocidal activity as potential pro prodrug models for the primary amino group containing 8-quinolinamines (5). The most effective pro prodrug analogue (6c) has displayed promising activities against drug-sensitive and drug-resistant strains of Plasmodia in vivo. 相似文献
110.
Cytokine control of memory B cell homing machinery 总被引:4,自引:0,他引:4
The germinal center (GC) is a pivotal site for the development of B cell memory. Whereas GC B cells do not chemotax to most chemokines and do not express the adhesion receptors L-selectin, alpha(4)beta(7), and cutaneous lymphocyte Ag (CLA), memory B cells respond to various chemotactic signals and express adhesion receptors. In this study, we show that CD40 ligand, IL-2, and IL-10 together drive this transition of GC B cells to memory phenotype in vitro, up-regulating memory B cell markers, chemotactic responses to CXC ligand (CXCL)12, CXCL13, and CCL19, and expression of adhesion receptors L-selectin, alpha(4)beta(7), and CLA. Moreover, addition of IL-4 modulates this transition, preventing chemotactic responses to CXCL12 and CXCL13 (but not to CCL19), and inhibiting the re-expression of L-selectin, but not of CLA or alpha(4)beta(7). CCR7 expression, responsiveness to CCL19, and L-selectin/alpha(4)beta(7) phenotype are coordinately regulated. Thus, IL-2/IL-10 and IL-4 play important and distinctive roles in developing the migratory capacities of memory B cells. 相似文献