scholarly journals Modulation of Leishmania ABC Protein Gene Expression through Life Stages and among Drug-Resistant Parasites

2006 ◽  
Vol 5 (10) ◽  
pp. 1713-1725 ◽  
Author(s):  
Philippe Leprohon ◽  
Danielle Légaré ◽  
Isabelle Girard ◽  
Barbara Papadopoulou ◽  
Marc Ouellette

ABSTRACT The ATP-binding cassette (ABC) protein superfamily is one of the largest evolutionarily conserved families and is found in all kingdoms of life. The recent completion of the Leishmania genome sequence allowed us to analyze and classify its encoded ABC proteins. The complete sequence predicts a data set of 42 open reading frames (ORFs) coding for proteins belonging to the ABC superfamily, with representative members of every major subfamily (from ABCA to ABCH) commonly found in eukaryotes. Comparative analysis showed that the same ABC data set is found between Leishmania major and Leishmania infantum and that some orthologues are found in the genome of the related parasites Trypanosoma brucei and Trypanosoma cruzi. Customized DNA microarrays were made to assess ABC gene expression profiling throughout the two main Leishmania life stages. Two ABC genes (ABCA3 and ABCG3) are preferentially expressed in the amastigote stage, whereas one ABC gene (ABCF3) is more abundantly expressed in promastigotes. Microarray-based expression profiling experiments also revealed that three ABC genes (ABCA3, ABCC3, and ABCH1) are overexpressed in two independent antimony-resistant strains compared to the parental sensitive strain. All microarray results were confirmed by real-time reverse transcription-PCR assays. The present study provides a thorough phylogenic classification of the Leishmania ABC proteins and sets the basis for further functional studies on this important class of proteins.

2009 ◽  
Vol 2009 (2) ◽  
pp. 206-212 ◽  
Author(s):  
Xiu-Mei SHENG ◽  
Xin-Xiang HUANG ◽  
Ling-Xiang MAO ◽  
Chao-Wang ZHU ◽  
Shun-Gao XU ◽  
...  

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii343-iii343
Author(s):  
Aaron M Taylor ◽  
Jianhe Shen ◽  
Lingzhao Ren ◽  
Keita Terashima ◽  
Lei Huang ◽  
...  

Abstract Intracranial germ cell tumors (IGCTs) account for 3% of CNS tumors in children in the U.S. and 11% in Japan and East Asian countries. IGCTs are separated into two distinct subtypes based on histology: germinomas and non-germinomatous germ cell tumors (NGGCTs). The deep central location of IGCTs makes surgical resection and therefore molecular subtype classification difficult, and previous gene expression studies are limited. We performed mRNA expression profiling (Human Genome U133 Plus 2.0) and microRNA expression profiling (ABI TaqMan) with 36 and 49 IGCTs, respectively. Sample stratification using non-negative matrix factorization clustering of gene expression revealed two distinct subgroups that delineated germinomas from NGGCTs. Employing stepwise model building in each data set separately, we were able to separate these groups using only mRNA probes for the LIN28B and L1TD1 genes, and two microRNA, microRNA-26a and microRNA-373. MicroRNA26a suppresses the LIN28B gene and is down-regulated in germinoma. LIN28B directly binds and suppresses the let-7 microRNA family, which suppress the KRAS oncogene, previously found to be mutated in ~19% of IGCTs. L1TD1 is required for human stem cell renewal and directly interacts with LIN28B for its RNA binding function. LIN28B and L1TD1 are both known to be upregulated in other systemic germ cell tumors, but this has not yet been documented in IGCTs. In conclusion, these results show that intracranial germinomas have similar gene expression compared to systemic seminoma, and suggest a mechanism by which activation of LIN28B and L1TD1 downregulates the let-7 microRNA and subsequently upregulates KRAS.


10.1038/14336 ◽  
1999 ◽  
Vol 23 (S3) ◽  
pp. 54-54
Author(s):  
Claire Johnson ◽  
Frank Burslem ◽  
Jerry Lanfear

Author(s):  
Kyonoshin Maruyama ◽  
Kazuko Yamaguchi-Shinozaki ◽  
Kazuo Shinozaki

2006 ◽  
Vol 8 (2) ◽  
pp. 183-192 ◽  
Author(s):  
Changqing Ma ◽  
Maureen Lyons-Weiler ◽  
Wenjing Liang ◽  
William LaFramboise ◽  
John R. Gilbertson ◽  
...  

2009 ◽  
Vol 15 (5) ◽  
pp. 509-521 ◽  
Author(s):  
Naoki Hama ◽  
Yuka Yanagisawa ◽  
Keizo Dono ◽  
Shogo Kobayashi ◽  
Shigeru Marubashi ◽  
...  

2011 ◽  
Vol 43 (3) ◽  
pp. 148-160 ◽  
Author(s):  
Stefania M. C. Simeone ◽  
Melissa W. Li ◽  
Pierre Paradis ◽  
Ernesto L. Schiffrin

Endothelin (ET)-1 plays an important pathophysiological role in several vascular diseases including hypertension and atherosclerosis. Transgenic mice overexpressing human preproET-1 selectively in the endothelium (eET-1) exhibit vascular injury in the absence of blood pressure elevation. ET-1 overexpression may induce vascular injury by inducing changes in gene expression. To understand mechanisms whereby ET-1 induces vascular damage, vascular gene expression profiling was performed using DNA microarrays. RNA from mesenteric arteries of male and female young (6–7 wk) and mature (6–8 mo) eET-1 and wild-type (WT) mice was isolated, and changes in gene expression were determined by genome-wide expression profiling using Illumina microarray and FlexArray software. Data were analyzed using a relaxed and a stringent statistical approach. The gene lists were compared and analyzed as well with Ingenuity Pathway Analysis. The most common change was an increase in the expression of lipid metabolism genes. Four of these genes were validated by qPCR, cyp51, dgat2, and scd1 genes in young and elovl6 in both young and mature male mice, supporting a role of ET-1 in atherosclerosis. To test the hypothesis that ET-1 participates in mechanisms leading to atherosclerosis, we crossed eET-1 with atherosclerosis-prone apoE−/− mice to determine whether ET-1 overexpression exacerbates high-fat diet (HFD)-induced atherosclerosis using oil red O staining of descending thoracic aorta. HFD increased lipid plaques by 3-, 27-, and 86-fold in eET-1, apoE−/−, and crossed mice, respectively, vs. WT. This suggests that increased endothelial ET-1 expression results in early changes in gene expression in the vascular wall that enhance lipid biosynthesis and accelerate progression of atherosclerosis.


2004 ◽  
Vol 17 (2) ◽  
pp. 140-149 ◽  
Author(s):  
Julian L. Griffin ◽  
Stephanie A. Bonney ◽  
Chris Mann ◽  
Abdul M. Hebbachi ◽  
Geoff F. Gibbons ◽  
...  

In functional genomics, DNA microarrays for gene expression profiling are increasingly being used to provide insights into biological function or pathology. To better understand the significance of the multiple transcriptional changes across a time period, the temporal changes in phenotype must be described. Orotic acid-induced fatty liver disease was investigated at the transcriptional and metabolic levels using microarrays and metabolic profiling in two strains of rats. High-resolution 1H-NMR spectroscopic analysis of liver tissue indicated that Kyoto rats compared with Wistar rats are predisposed to the insult. Metabolite analysis and gene expression profiling following orotic acid treatment identified perturbed metabolic pathways, including those involved in fatty acid, triglyceride, and phospholipid synthesis, β-oxidation, altered nucleotide, methyl donor, and carbohydrate metabolism, and stress responses. Multivariate analysis and statistical bootstrapping were used to investigate co-responses with transcripts involved in metabolism and stress responses. This reverse functional genomic strategy highlighted the relationship between changes in the transcription of stearoyl-CoA desaturase 1 and those of other lipid-related transcripts with changes in NMR-derived lipid profiles. The results suggest that the integration of 1H-NMR and gene expression data sets represents a robust method for identifying a focused line of research in a complex system.


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