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Exon I (exon + i)
Selected AbstractsIdentification of a novel human tissue factor splice variant that is upregulated in tumor cells,INTERNATIONAL JOURNAL OF CANCER, Issue 7 2006Hitendra S. Chand Abstract Tissue factor (TF) is a transmembrane glycoprotein that serves as the prime initiator of blood coagulation and plays a critical role in thrombosis and hemostasis. In addition, a variety of tumor cells overexpress cell-surface TF, which appears to be important for tumor angiogenesis and metastasis. To elucidate the mechanism involved in the upregulation of TF in human tumor cells, a comprehensive analysis of TF mRNA from various normal and tumor cells was performed. The results of these studies indicate that, in addition to possessing a normal full-length TF transcript and minor levels of an alternatively spliced transcript known as alternatively-spliced tissue factor (asTF) (Bogdanov et al., Nat Med 2003;9:458,62), human tumor cells express additional full-length TF transcripts that are also generated by alternative splicing. Reverse transcriptase-polymerase chain reaction (RT-PCR) and 5,-rapid amplification of cDNA ends- (5,-RACE) based analyses of cytoplasmic RNA from normal and tumor cells revealed that there is alternative splicing of the first intron between exon I and exon II resulting in 2 additional TF transcripts. One of the transcripts has an extended exon I with inclusion of most of the first TF intron (955 bp), while the second transcript is formed by the insertion of a 495 bp sequence, referred to as exon IA, derived from an internal sequence of the first intron. The full length TF transcript with alternatively spliced novel exon IA, referred to as alternative exon 1A-tissue factor (TF-A), represented ,1% of the total TF transcripts in normal cells, but constituted 7,10% of the total TF transcript in tumor cells. Quantitative real-time RT-PCR analysis indicated that cultured human tumor cells contain 10,25-fold more copy numbers of TF-A in comparison to normal, untransformed cells. We propose that high-level expression of the novel TF-A transcript, preferentially in tumor cells, may have utility in the diagnosis and staging of a variety of solid tumors. © 2005 Wiley-Liss, Inc. [source] Age-Dependent Changes in the Calcium Sensitivity of Striatal Mitochondria in Mouse Models of Huntington's DiseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2005N. Brustovetsky Abstract Striatal and cortical mitochondria from knock-in and transgenic mutant huntingtin mice were examined for their sensitivity to calcium induction of the permeability transition, a cause of mitochondrial depolarization and ATP loss. The permeability transition has been suggested to contribute to cell death in Huntington's Disease. Mitochondria were examined from slowly progressing knock-in mouse models with different length polyglutarnine expansions (Q20, Q50, Q92, Q111) and from the rapidly progressing transgenic R6/2 mice overexpressing exon I of human huntingtin with more than 110 polyglutamines. As previously observed in rats, striatal mitochondria from background strain CD1 and C57BL/6 control mice were more sensitive to calcium than cortical mitochondria. Between 5 and 12 months in knock-in Q92 mice and between 8 and 12 weeks in knock-in Q111 mice, striatal mitochondria developed resistance, becoming equally sensitive to calcium as cortical mitochondria, while those from Q50 mice were unchanged. Cortical mitochondrial calcium sensitivity did not change. In R6/2 mice striatal and cortical mitochondria were equally resistant to Ca2+ while striatal mitochondria from littermate controls were more susceptible. No increases in calcium sensitivity were observed in the mitochondria from Huntington's Disease (HD) mice compared to controls. Neither motor abnormalities, nor expression of cyclophilin D corresponded to the changes in mitochondrial sensitivity. Polyglutamine expansions in huntingtin produced an early increased resistance to calcium in striatal mitochondria suggesting mitochondria undergo compensatory changes in calcium sensitivity in response to the many cellular changes wrought by polyglutamine expansion. [source] Characterization of an I,B-like gene in Cotesia vestalis polydnavirusARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 2 2008Ya-Feng Chen Abstract Cotesia vestalis (Braconidae, Hymenoptera) depends mainly on 3 regulatory factors to manipulate its host's development and immune response, including polydnavirus, venom, and teratocytes, among which polydnavirus plays a key role in suppressing the host immune system. In the present work, we cloned the full sequence of gene CvBV-ank2, encoding an I,B-like protein in C. vestalis polydnavirus (CvBV). The full sequence of CvBV-ank2 is 955 bp, encoding 162 amino acids with a calculated molecular mass of 18,355 Da. CvBV-ank2 shares high similarity with the exon I and exon II of CvBV-ank1, which is on the same segment with CvBV-ank2. This result suggests that gene duplication might occur in CvBV-ank1 and CvBV-ank2. Phylogenetic analysis indicated that CvBV-ank2 and CvBV-ank1, both on segment CvBV-S2, are, respectively, closely related with CcBV,26.3 and CcBV,26.2, both on segment Circle26 of C. congregata polydnavirus (CcBV). BLAST search using the sequence of segment CvBV-S2 as a query revealed that segment CvBV-S2 shares 90% max identity with segment Circle26 of CcBV over 67% query coverage. These results demonstrate that there is not only gene similarity, but also segment similarity between CvBV and CcBV. Transcripts of CvBV-ank2 were detected as early as 0.5 h post-parasitization and continued to be detected for 6 days, indicating that CvBV-ank2 might be involved in the early protection of the parasitoid egg. Arch. Insect Biochem. Physiol. 2008. © 2008 Wiley-Liss, Inc. [source] Changes in alternative brain-derived neurotrophic factor transcript expression in the developing human prefrontal cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2009Jenny Wong Abstract In this study, we determined when and through which promoter brain-derived neurotrophic factor (BDNF) transcription is regulated during the protracted period of human frontal cortex development. Using quantitative real-time polymerase chain reaction, we examined the expression of the four most abundant alternative 5, exons of the BDNF gene (exons I, II, IV, and VI) in RNA extracted from the prefrontal cortex. We found that expression of transcripts I,IX and VI,IX was highest during infancy, whereas that of transcript II,IX was lowest just after birth, slowly increasing to reach a peak in toddlers. Transcript IV,IX was significantly upregulated within the first year of life, and was maintained at this level until school age. Quantification of BDNF protein revealed that levels followed a similar developmental pattern as transcript IV,IX. In situ hybridization of mRNA in cortical sections showed the highest expression in layers V and VI for all four BDNF transcripts, whereas moderate expression was observed in layers II and III. Interestingly, although low expression of BDNF was observed in cortical layer IV, this BDNF mRNA low-zone decreased in prominence with age and showed an increase in neuronal mRNA localization. In summary, our findings show that dynamic regulation of BDNF expression occurs through differential use of alternative promoters during the development of the human prefrontal cortex, particularly in the younger age groups, when the prefrontal cortex is more plastic. [source] | ||||||||||