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Results for “tissue specificity”

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At least 253 records · Page 14Linked to original sources

PubMed1986

Intermediate filament proteins as tissue specific markers in normal and malignant urological tissues.

Immunocytochemical techniques have become valuable tools in many fields of clinical pathology and medical research. Especially the development of highly specific (monoclonal) antibodies to a large variety of tissue antigens has in recent years led to the establishment of sensitive tissue markers. One of the most promising types of tissue specific markers so far is represented by the intermediate filament proteins. Since the findings of this rapidly expanding field are also being applied in urology, we have reviewed the current data in order to describe the new insights in tumor biology and histogenesis, as well as their application in diagnostic pathology.

Animals↗

PubMed2000

Tissue specific expression of PKR protein kinase in aging B6D2F1 mice.

A decline in the rate of protein synthesis is a common biochemical change observed with aging in a wide variety of cells and organisms. The double stranded RNA-dependent protein kinase PKR has been shown to phosphorylate eukaryotic initiation factor 2 alpha (eIF-2alpha), a well-characterized factor for down-regulating protein synthesis, in response to environmental stress conditions. Therefore, we were interested in evaluating the role of PKR in the aging process. Tissues from 2- and 20-month-old B6D2F1 male mice were evaluated by Western blot analysis. PKR was detected in all tissues of aging mice confirming its ubiquitous nature. Tissues examined from young mice showed little evidence of PKR expression, suggesting an age-associated up-regulation. P58(IPK), a cellular inhibitor of PKR, was expressed in tissues from both age groups but to a greater extent in tissues of aging mice suggesting an up-regulation to control PKR activity. Hyperphosphorylated eIF-2alpha was increased in selected tissues from older mice compared with tissues from younger mice indicating a possible correlation between PKR expression and kinase function. The data suggest that translational activity is slowing down in a tissue specific manner during the aging process in mice, possibly as the result of increased levels of PKR, and could be a factor in the reduction of the rate of protein synthesis during senescence seen in specific tissues of many organisms.

Aging↗

PubMed2005

Tissue-dependent isoforms of mammalian Fox-1 homologs are associated with tissue-specific splicing activities.

An intronic hexanucleotide UGCAUG has been shown to play a critical role in the regulation of tissue-specific alternative splicing of pre-mRNAs in a wide range of tissues. Vertebrate Fox-1 has been shown to bind to this element, in a highly sequence-specific manner, through its RNA recognition motif (RRM). In mammals, there are at least two Fox-1-related genes, ataxin-2 binding protein 1 (A2BP1)/Fox-1 and Fxh/Rbm9, which encode an identical RRM. Here, we demonstrate that both mouse Fxh and A2BP1 transcripts undergo tissue-specific alternative splicing, generating protein isoforms specific to brain and muscle. These tissue-specific isoforms are characterized for their abilities to regulate neural cell-specific alternative splicing of a cassette exon, N30, in the non-muscle myosin heavy chain II-B pre-mRNA, previously shown to be regulated through an intronic distal downstream enhancer (IDDE). All Fxh and A2BP1 isoforms with the RRM are capable of binding to the IDDE in vitro through the UGCAUG elements. Each isoform, however, shows quantitative differences in splicing activity and nuclear distribution in transfected cells. All Fxh isoforms and a brain isoform of A2BP1 show a predominant nuclear localization. Brain isoforms of both Fxh and A2BP1 promote N30 splicing much more efficiently than do the muscle-specific isoforms. Skeletal muscles express additional isoforms that lack a part of the RRM. These isoforms are incapable of activating neural cell-specific splicing and, moreover, can inhibit UGCAUG-dependent N30 splicing. These findings suggest that tissue-specific isoforms of Fxh and A2BP1 play an important role in determining tissue specificity of UGCAUG-mediated alternative splicing.

Alternative Splicing↗

PubMed1993

Tissue-specific promoters regulate aromatase cytochrome P450 expression.

In the human, estrogen biosynthesis occurs in several tissue sites, including ovary, placenta, adipose, and brain. Recent work from our laboratory has indicated that tissue-specific expression of aromatase cytochrome P450 (P450arom), the enzyme responsible for estrogen biosynthesis, is determined, in part, by the use of tissue-specific promoters. Thus the expression of P450arom in human ovary appears to utilize a promoter proximal to the translation start-site. This promoter is not utilized in placenta but instead, the promoter used to drive aromatase expression in placenta is at least 40 kb upstream from the translational start-site. In addition, there is a minor promoter used in the expression of a small proportion of placental transcripts which is 9 kb upstream from the start of translation. Transcripts from these promoters are also expressed in other fetal tissues including placenta-related cells such as JEG-3 choriocarcinoma cells, hydatidiform moles, and other fetal tissues such as fetal liver. On the other hand, in adipose tissue expression of P450arom may be achieved by yet another, adipose-specific promoter. The various 5'-untranslated exons unique for expression driven by each of these promoters are spliced into a common intron/exon boundary upstream from the translational start-site. This means that the protein expressed in each of the various tissue-specific sites of estrogen biosynthesis is identical.

Amino Acid Sequence↗

PubMed2001

Role of integrin alphaE(CD103)beta7 for tissue-specific epidermal localization of CD8+ T lymphocytes.

Tissue-specific T cell localization is crucial for immune surveillance of normal tissues and the pathogenesis of inflammatory disorders. In psoriatic skin, CD8+ lymphocytes predominantly reside within the epidermis, whereas CD4+ T cells are most abundant within the dermis. Molecular mechanisms guiding this spatial compartmentalization are not completely understood, however. Here, we demonstrate that 55% (+/-9.7%, n = 14) of the epidermal T cells, predominantly of the CD8+ phenotype, expressed the integrin alphaE(CD103)beta7. In contrast, only 5% (+/-2.0%) of the dermal T cells were alphaE(CD103)beta7+. Integrin alphaE(CD103)beta7 was not detected in normal skin (n = 10), and less than 1% of peripheral blood lymphocytes derived from normal (n = 11) or psoriatic (n = 10) donors expressed alphaE(CD103). When cultured T lymphoblasts (n = 12 donors) were stimulated with transforming growth factor beta1, expression of integrin alphaE(CD103)beta7 was induced on 52.8% (+/-16.2%) of CD8+ cells, but only on 6.1% (+/-2.3%) of CD4+ cells, suggesting selective inducibility on CD8+ lymphocytes. Whereas similar overall expression of transforming-growth-factor-beta1-specific mRNA was detected in normal and psoriatic skin by real-time quantitative polymerase chain reaction, immunohistochemistry revealed focal overexpression of transforming growth factor beta1 underneath psoriatic, but not normal, epidermis. This heterogenous transforming growth factor beta1 expression may contribute to induction of alphaE(CD103) in vivo. Adhesion of transforming-growth-factor-beta1-stimulated CD8+, but not CD4+, T cells to cultured keratinocytes and psoriatic epidermis in frozen sections could be significantly inhibited by antibodies that blocked the alphaE(CD103)/E-cadherin interaction. Co-culture of lymphoblasts and keratinocytes resulted in marginal enhancement of alphaE(CD103)beta7 expression in some cases. Overall, integrin alphaE(CD103)beta7 appears to contribute to tissue-specific epidermal localization of CD8+ T lymphocytes.

Antigens, CD↗

PubMed1986

Thyroid hormone regulation of malic enzyme synthesis. Dual tissue-specific control.

The regulatory mechanism(s) involved in the tissue-specific induction of cytosolic malic enzyme (EC 1.1.1.40) by triiodothyronine (T3) have been investigated in rat liver and heart. In these two tissues, cellular malic enzyme mRNA accumulates to different extents in response to hormonal stimulation (11-16- and 3-4-fold above the respective basal levels) (Dozin, B., Magnuson, M. A., and Nikodem, V. M. (1985) Biochemistry 24, 5581-5586). To gain further insight into this pretranslational control, nuclear in vitro run-off transcription assays were performed and correlated with the levels of malic enzyme RNA sequences in cytoplasm. The data demonstrate that the rate of transcription of the malic enzyme gene is stimulated by T3 to similar extents in liver and heart (3-4-fold above the basal activity). In liver, T3 also promotes an additional increase in cellular malic enzyme mRNA. This additional effect could be due to a tissue-specific change in the rate of degradation of cytoplasmic mRNA or to an effect on malic enzyme mRNA in the nucleus.

Animals↗

PubMed2004

Role of enzymes and tissue-specific actions of steroids.

Enzymes, such as steroid sulphatase, sulphotransferases and 17 beta-hydroxydehydrogenases, are important in regulating the tissue-specific actions of steroids. These enzymes can exist in different isoforms in different tissues and can be regulated by tissue-specific promoters and factors such as cytokines, prostaglandins and growth factors. The activity of these enzymes and the mechanisms by which they are regulated may help to account for some of the tissue-specific effects of the hormone replacement therapy drug tibolone, which has oestrogenic effects on the bone but not on the breast or endometrium.

Bone and Bones↗

PubMed1996

Differential pattern in tissue-specific somatic mosaicism of expanded CAG trinucleotide repeats in dentatorubral-pallidoluysian atrophy, Machado-Joseph disease, and X-linked recessive spinal and bulbar muscular atrophy.

We investigated the somatic mosaicism of trinucleotide repeat expansion in the neural and nonneural tissues of a dentatorubral-pallidoluysian atrophy (DRPLA), Machado-Joseph disease (MJD), and spinal and bulbar muscular atrophy (SBMA) patient and their correlation to the topographical distribution of the pathological involvement. The spatial pattern of tissue-specific somatic mosaicism in the CAG repeat size was significantly different among the DRPLA, MJD and SBMA patients. The size of the major bands of the mutant CAG repeat allele was significantly smaller in the cerebellar cortex in both DRPLA and MJD patients by 6 and 2 repeat units respectively and larger in the colon and liver of DRPLA by 5 repeats or more. There were also 1-2 repeat-sized small variations of major band size among the neural tissues in DRPLA. In contrast, there was no tissue-specific variation of major bands of CAG repeats and diversity of extra bands among the examined tissues including the cerebellum in the SBMA patient. There was no parallel occurrence of tissue-specific CAG instability and severity of neuropathological involvement in the neural and nonneural tissues of DRPLA, MJD and SBMA patients. Lack of significant tissue-specific somatic mosaicism in SBMA including the cerebellar cortex may suggest that CAG repeat expansion in the mutant androgen receptor gene is far more stable compared with that in DRPLA and MJD as well as those reported in Huntington's disease.

Adult↗

PubMed1984

Tissue specificity of the heat-shock response in maize.

The tissue specificity of the heat-shock response in maize was investigated. The ability to synthesize heat shock proteins (hsp) at 40 degrees C, as well as the intensity and duration of that synthesis, was analyzed in coleoptiles, scutella, green and etiolated leaves, suspension-cultured cells, germinating pollen grains, and primary root sections at different stages of development. One-dimensional sodium dodecyl sulfate gel electrophoresis of extracted proteins revealed that most of the tissues synthesized the typical set of 10 hsp, but that the exact characteristics of the response depended upon the tissue type. While elongating portions of the primary root exhibited a strong heat shock response, the more mature portions showed a reduced ability to synthesize hsp. Leaves, whether green or etiolated, excised or intact, constitutively synthesized a low level of hsp at 25 degrees C, and high levels could be induced at 40 degrees C. Suspension-cultures of Black Mexican sweet corn synthesized, besides the typical set of hsp, two additional polypeptides. In contrast to all the other tissues, germinating pollen grains could not be induced to synthesize the typical set of hsp but did synthesize two new polypeptides of 92 and 56 kD molecular weight.The heat shock response was transient for most of the tissues which synthesized the standard set of hsp. Hsp synthesis was detected up to 2 to 3 hours, but not at 10 hours of continuous 40 degrees C treatment. The exception was suspension cultured cells, in which hsp synthesis showed only a slight reduction after 10 hours at 40 degrees C. Tissue-specific differences in the heat-shock response suggest that there are differences in the way a given tissue is able to adapt to high temperature.We have confirmed the previous suggestion that maize hsp do not accumulate in substantial quantities. Using two-dimensional gel analysis, hsp could be detected by autoradiography but not by sensitive silver staining techniques.

Journal Article↗

PubMed1994

A possible link between molecular evolution and tissue evolution demonstrated by tissue specific genes.

In this paper, we reviewed our recent works on a possible link between molecular evolution and tissue evolution. The evolutionary rates of genes that are expressed tissue specifically were shown to differ widely to one another, depending on tissues: Brain specific genes evolve with significantly slower rate than immune specific genes. The tissue dependence of molecular evolutionary rate strongly suggests the presence of functional constraints against molecular changes from tissue level. A molecular phylogenetic analysis of tissue specific isoforms that are identical to one another in function, but differ only in tissue distribution revealed frequent gene duplications and rapid accumulations of amino acid substitutions during the early evolution of chordates, where rapid evolution at the tissue or organ levels is thought to have occurred. On the basis of functional constraints, a possible explanation for the correlation between evolution at the two levels was presented.

Animals↗

PubMed2005

Identification of regulatory targets of tissue-specific transcription factors: application to retina-specific gene regulation.

Identification of tissue-specific gene regulatory networks can yield insights into the molecular basis of a tissue's development, function and pathology. Here, we present a computational approach designed to identify potential regulatory target genes of photoreceptor cell-specific transcription factors (TFs). The approach is based on the hypothesis that genes related to the retina in terms of expression, disease and/or function are more likely to be the targets of retina-specific TFs than other genes. A list of genes that are preferentially expressed in retina was obtained by integrating expressed sequence tag, SAGE and microarray datasets. The regulatory targets of retina-specific TFs are enriched in this set of retina-related genes. A Bayesian approach was employed to integrate information about binding site location relative to a gene's transcription start site. Our method was applied to three retina-specific TFs, CRX, NRL and NR2E3, and a number of potential targets were predicted. To experimentally assess the validity of the bioinformatic predictions, mobility shift, transient transfection and chromatin immunoprecipitation assays were performed with five predicted CRX targets, and the results were suggestive of CRX regulation in 5/5, 3/5 and 4/5 cases, respectively. Together, these experiments strongly suggest that RP1, GUCY2D, ABCA4 are novel targets of CRX.

Animals↗

PubMed2006

Analysis of tissue-specific differentially methylated regions (TDMs) in humans.

Alterations in DNA methylation have been implicated in mammalian development. Hence, the identification of tissue-specific differentially methylated regions (TDMs) is indispensable for understanding its role. Using restriction landmark genomic scanning of six mouse tissues, 150 putative TDMs were identified and 14 were further analyzed. The DNA sequences of the 14 mouse TDMs are analyzed in this study. Six of the human homologous regions show TDMs to both mouse and human and genes in five of these regions have conserved tissue-specific expression: preferential expression in testis. A TDM, DDX4, is further analyzed in nine testis tissues. An increase in methylation of the promoter region is significantly associated with a marked reduction of the gene expression and defects in spermatogenesis, suggesting that hypomethylation of the DDX4 promoter region regulates DDX4 gene expression in spermatogenic cells. Our results indicate that some genomic regions with tissue-specific methylation and expression are conserved between mouse and human and suggest that DNA methylation may have an important role in regulating differentiation and tissue-/cell-specific gene expression of some genes.

Aged↗

PubMed2000

Modulation of adriamycin toxicity by tissue-specific induction of metallothionein synthesis in mice.

The effect of tissue specific induction of metallothionein (MT) by preadministration of metal compounds on the antitumor activity and adverse effects of adriamycin (ADR) was examined using mice bearing colon 38 adenocarcinoma. Significant increase in MT concentration was observed in the heart and bone marrow but not in the tumor tissue of the mice given bismuth (Bi) compound. Copper (Cu) increased MT in the tumor tissue but did not induce MT either in bone marrow or in the heart, whereas zinc (Zn) increased MT level in the heart and bone marrow as well as in the tumor tissue. ADR exerted cardiotoxicity, indicated by increase in lipid peroxidation in the heart, bone marrow toxicity, indicated by decrease in number of peripheral leukocytes, and antitumor activity, assessed by reduction of tumor weight, in tumor-bearing mice untreated with MT inducing metal compounds. Preadministration of Bi significantly reduced the cardiotoxicity and bone marrow toxicity without compromising the antitumor activity of ADR. Cu pretreatment did not affect the extent of cardiotoxicity and bone marrow toxicity but significantly suppressed the antitumor effect. Pretreatment with Zn markedly reduced not only the adverse side effects but also the antitumor activity. The results described above suggest that ADR toxicity can be attenuated in the tissues in which the MT level was elevated and that the tissue specific induction of MT synthesis may provide a promising regimen for cancer chemotherapy.

Animals↗

PubMed1980

Tissue specificity of enzyme expression regulated by diffusible factors: evidence in Drosophila hybrids.

Pairs of hybridizable species of Hawaiian picture-winged Drosophila differ qualitatively in the distributions of specific enzymes in their tissues. An examination of the patterns of enzyme expression in the hybrids showed that, in three instances, absence of an enzyme from a specific tissue was dominant to presence. Since other developmental features indicated that both parental genomes were functioning, these results suggest that, in these cases, the pattern differences in the parental species were due to diffusible factors that affected expression of the relevant structural genes rather than to differences in the genes themselves or in cis-acting regulatory sites.

Adipose Tissue↗

PubMed1997

Porcine aromatases: studies on tissue-specific, functionally distinct isozymes from a single gene?

Aromatase cytochrome P450 (P450arom) is expressed in a variety of tissues. Pigs express P450arom as bilaminar blastocysts in utero, and thereafter in the gonads, adrenal glands and placenta. Our studies also demonstrate the existence of porcine isozymes of P450arom which differ substantially in their amino acid composition and function. The placental isoform, most similar to P450arom in other mammals, consists of 503 amino acids. The ovarian isoform, expressed in both theca and granulosa cells, is a 501 amino acid protein exhibiting less than 20% of the activity of the placental isozyme. Furthermore, it is inhibited not only by CGS16949A but also by etomidate which does not inhibit the placental P450arom. Partial sequences generated by the rapid amplification of the cDNA ends (RACE) procedure indicate that the expression of a third isoform in the blastocyst is switched to the placental isozyme during differentiation of the fetal membranes. In addition, these transcripts, and others from the theca, granulosa, testes, adrenal glands and placenta demonstrate differences in the 5'-untranslated region (putative exon I) suggestive of tissue-specific alternative splicing. An identical 5'-untranslated sequence was obtained from transcripts expressed in the theca and granulosa. Testes and adrenal transcripts also have identical 5' ends, which differ substantially from the ovarian sequence. Blastocyst and placenta 5'-untranslated sequences differ from each other and from those expressed in the gonads and adrenals. Several tissue-specific transcripts thus encode porcine P450arom. Interestingly, distinct 5' sequences exist for ovarian and testes P450arom mRNAs, suggesting different promoters and therefore regulation in the male and female gonads. The molecular origins of the functional isoforms and the tissue-specific transcripts are uncertain, however partial genomic sequence and other genetic analyses suggest the existence of multiple genes. However, sequence alignment of the placental and ovarian isoforms indicates complete conservation of putative exon III, so that complex splicing remains a possibility. Clearly, the regulation of P450arom expression is more complex in the pig than in other vertebrates investigated to date.

Amino Acid Sequence↗

PubMed1992

The human colipase gene: isolation, chromosomal location, and tissue-specific expression.

The digestion of dietary triglycerides occurs in the duodenum through the action of triglyceride lipase, a pancreatic exocrine protein. The activity of pancreatic lipase is inhibited by the bile salts normally found in the gut lumen. Another pancreatic exocrine protein, colipase, restores the lipolytic activity of triglyceride lipase. The synthesis and secretion of both triglyceride lipase and colipase is increased by dietary fats and secretin. An increase in mRNA accompanies the increased activity, suggesting that the genes for triglyceride lipase and colipase contain nucleotide elements responsive to dietary fats or secretin or both. To study the regulation of colipase expression, we have first isolated the gene for human colipase from a cosmid library with a cDNA probe. The gene was localized to chromosome 6 and is organized into three exons contained in a single 3.3-kb BamHI fragment. The 5'-flanking region of the gene contains a TATA box, a GC box, and a 28-bp region with homology to the rat pancreatic-specific enhancer. This region directs the tissue-specific expression of the chloramphenicol acetyltransferase gene in a transfected rat pancreatic acinar cell line, AR42-J. The same construct is inactive in HEPG2, C2C12, and COS-1 cells. These results demonstrate that the isolated gene for human colipase contains tissue-specific promoter activity in the 5'-flanking DNA. The 28-bp region specifically binds to a factor in nuclear extracts.

Amino Acid Sequence↗

PubMed2000

Characterisation and tissue-specific expression of the two keratin subfamilies of intermediate filament proteins in the cephalochordate Branchiostoma.

The cloning of three intermediate filament proteins expressed at the gastrula stage (kl, Y1, X1) extends the size of the IF multigene family of Branchiostoma to at least 13 members. This is one of the largest protein families established for the lancelet. Sequence comparisons indicate five keratin orthologs, three of type I (E1, k1, Y1) and two of type II (E2, D1). This assignment is confirmed by the obligatory heteropolymeric polymerisation behaviour of the recombinant proteins. In line with the hetero-coiled-coil principle IF are formed by any stoichiometric mixture of type I and II keratin orthologs. In spite of the strong sequence drift chimeric IF are formed between K8, a human keratin II, and two of the lancelet type I keratins. We discuss whether the remaining 8 IF proteins reflect three additional and potentially cephalochordate-specific subfamilies. The tissue-specific expression patterns of the 5 keratins and some other IF proteins were analysed by immunofluorescence in the adult. Keratins are primarily present in ectodermally derived tissues. Developmental control of the expression of some IF proteins is observed, but three keratins (k1, Y1, D1) and an additional IF protein (X1) detected at the gastrula stage are expressed throughout the life cycle.

Amino Acid Sequence↗

PubMed1989

Developmental and tissue-specific regulation of a novel transcription factor of the sea urchin.

We have identified a novel transcription factor that interacts with the promoter of four tissue-specific late histone H2A-2 and H2B-2 genes of the sea urchin by DNase I footprint, mobility shift, and methylation interference analyses. The binding site for this factor is required for efficient transcription of the H2B-2.1 gene both in vitro in nuclear extracts of gastrula embryos and in vivo in microinjected sea urchin embryos. This factor binds with equal affinity to the recognition sequences of all four histone genes in cross-competition assays. Moreover, the binding site of the H2B-2.2 promoter can functionally substitute for that of the H2B-2.1 gene in in vivo expression experiments. Nevertheless, all four binding sites share little sequence homology with each other. This transcription factor increases in abundance during embryogenesis and has been detected in the adult sea urchin only in the tube feet, where the late H2A-2 and H2B-2 genes are expressed specifically. Therefore, we refer to this factor as tissue-specific activator protein (TSAP). The close correlation between the presence of TSAP and the expression pattern of the late H2A-2 and H2B-2 genes suggests that this transcription factor is directly responsible for the developmental and tissue-specific regulation of these genes.

Aging↗