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At least 127 records · Page 7Linked to original sources
PubMed2000

Isoform expression of the sarcoplasmic reticulum Ca2+ release channel (ryanodine channel) in human myocardium.

The Ca2+ release channel of the sarcoplasmic reticulum (SR) is essential for the release of Ca2+ from intracellular stores and is expressed widely in various excitable cells. It plays a key role particularly in excitation contraction coupling in myocytes in skeletal and cardiac muscle. Three isoforms of the SR Ca2+ release channel have been cloned. Recently coexpression of different isoforms was reported in different animal species and various tissues. In human cardiac tissue, however, isoform expression is not yet established. Therefore the aim of this study was to characterize isoform expression of the SR Ca2+ release channel in the human heart. We examined specific isoform expression of mRNA and proteins of the SR Ca2+ release channel in the four different chambers of the heart and the interventricular septum from explanted human hearts from nonfailing organ donors (n=8). Reverse transcriptase PCR from total cardiac RNA with isoform specific primers and western blots from myocardial homogenates with isoform specific antibodies were performed. Quantification of protein expression was achieved by densitometric scanning and computer analysis and is expressed as densitometric units per microgram of protein. A single band DNA signal was detected by reverse transcriptase PCR for the skeletal isoform 1 and the cardiac isoform 2 and isoform 3 in all regions of the human heart investigated. Specific protein expression was detected in all five myocardial regions of the human heart in western blots for the skeletal isoform I and cardiac isoform 2, and a weaker specific band was also detectable for isoform 3 of the SR Ca2+ release channel. Quantification of protein expression showed significant (P=0.008) lower expression of isoform 1 in the right ventricle (42+/-4 densitometric units/g tissue) and similar expression in all other regions (right atrium 58+/-3; septum 51+/-5, left atrium 54+/-5; left ventricle 51+/-6). Isoform 2 of the SR Ca2+ release channel was also significantly lower (P=0.001) in the right ventricle (33+/-4 densitometric/g tissue) and similar in the other heart chambers (right atrium 42+/-5: septum 41+/-3, left atrium 52+/-6, left ventricle 42+/-3). Differences in isoform 3 of the SR Ca2+ release channel for the various myocardial regions did not reach significant levels (right atrium 45+/-6, right ventricle 38+/-5, septum 49+/-8, left atrium 46+/-7, and in left ventricle 45+/-3 densitometric units/g tissue). In conclusion, all three isoforms of the SR Ca2+ release channel were determined in the human heart at both mRNA and protein levels with different quantitative expression in the different heart chambers. Coexpression of the three different isoforms with different functional properties might increase the complexity of regulation of excitation contraction coupling in the human heart in a chamber specific mode.

Adult↗
PubMed1993

Identification of an isoform of the estrogen receptor messenger RNA lacking exon four and present in the brain.

An isoform of the estrogen receptor messenger RNA (ER-mRNA) was identified in RNA from the brain of lizards and rats. Poly(A)+ RNA from brain and uteri was reverse transcribed using gene-specific primer for the ER. The resulting complementary DNA was amplified in a polymerase chain reaction followed by cloning and sequencing of the amplified products. This isoform lacks exon four and is designated delta 4 ER-mRNA. Although several isoforms of the ER have been described from cancerous cells, to our knowledge, none has been identified previously in the brain. Furthermore, the delta 4 isoform is the only isoform detected in normal tissue. The delta 4 isoform appeared most abundant in RNA from brain tissue, whereas uterine RNA contained only trace amounts of the isoform. Apparently, tissue-specific alternative splicing accounts for these differences in abundance. Because exon four encodes a part of the steroid-binding domain, we predict that the corresponding protein encoded by the isoform will not bind estradiol and may therefore belong to a growing subclass of the steroid/thyroid/vitamin superfamily known as orphan receptors. We predict that the putative delta 4 protein may function as a ligand-independent transcription factor that acts on the same DNA response elements as the conventional ER. The abundance of this isoform in the brain relative to the uterus raises fundamental questions regarding the regulation of estrogen-responsive genes in different tissues.

Animals↗
PubMed2001

Growth condition-dependent synchronized changes in transcript levels of type II hexokinase and type 1 glucose transporter in tumor cells.

Transcript levels of hexokinase (HK) isozymes and glucose transporter (GLUT) isoforms in RNA samples of AH130 cells obtained from dish cultures and ascites were evaluated in a quantitative manner. In AH130 cells cultured in dishes, HKI and HKII were expressed at a similar level, but HKIII and HKIV were not. GLUT1 and GLUT3 were also expressed, and messages of these two isoforms represented 27% and 71%, respectively, of the total GLUT messages. A faint signal of GLUT2 was also observed. On the contrary, in cells grown as ascites, the transcript of HKII was dominant, and its level was about 15-fold over that of dish-cultured AH130 cells. Transcript levels of GLUT1 and GLUT3 were 4.5- and 2-fold, respectively, higher than those in dish-cultured cells. Thus, GLUT1 was more susceptible to changes in culture conditions than GLUT3. Based on these results, we concluded that the change in growth conditions caused synchronized changes in the transcript levels of HKII and GLUT1 in AH130 cells. However, such marked changes in the transcript levels of HKII and GLUT1 were not observed when AH130 cells were cultured in dishes under a hypoxic condition, indicating that the observed changes were not solely attributable to the difference in oxygen concentration between the ascites and cell culture conditions. Accordingly, other factors such as growth factors may be responsible for this difference in levels of HKII and GLUT1 between the two growth conditions.

Animals↗
PubMed2001

Human angiotensin II type 1 receptor isoforms encoded by messenger RNA splice variants are functionally distinct.

Human tissues that express the angiotensin II (Ang II) type 1 receptor (hAT(1)R) can synthesize four distinct alternatively spliced hAT(1)R mRNA transcripts. In this study, we show that the relative abundance of these mRNA transcripts varies widely in human tissues, suggesting that each splice variant is functionally distinct. Here we demonstrate, for the first time, that the hAT(1)R-B mRNA splice variant encodes a novel long hAT(1)R isoform in vivo that has significantly diminished affinity for Ang II (i.e. >3-fold) when compared with the short hAT(1)R isoform (encoded by hAT(1)R-A mRNA splice variant). This reduced agonist affinity caused a significant shift to the right in the dose-response curve for Ang II-induced inositol trisphosphate production and Ca(2+) mobilization of the long hAT(1)R when compared with that of the short hAT(1)R. The functional differences between these isoforms allows Ang II responsiveness to be fine-tuned by regulating the relative abundance of the long and short hAT(1)R isoform expressed in a given human tissue.

Adrenal Cortex Neoplasms↗
PubMed1993

Regional distribution of the alternatively spliced isoforms of beta APP RNA transcript in the brain of normal, heterozygous and homozygous weaver mutant mice as revealed by in situ hybridization histochemistry.

The cellular localization of amyloid beta-protein precursor (beta APP) RNA transcripts was studied by in situ hybridization histochemistry in normal, heterozygous and homozygous weaver (wv) mutant mice, which lose midbrain dopamine (DA) neurons, cerebellar granule cells, and Purkinje cells. The beta APP gene is located at the distal end of mouse chromosome (MMU) 16, on which the wv locus has been assigned as well. Transcripts encoding isoforms beta APP695, beta APP714 and beta APP751 were present in several different brain areas of normal (+/+) mice, including hippocampus, substantia nigra (SN) pars compacta and cerebellum. The same transcripts were progressively reduced in homozygous weaver (wv/wv) SN, in correlation with DA neuron loss. The beta APP770 species--normally seen in striatum and not SN--was present in the mutant striatum. There were not any obvious changes in beta APP expression in the nigrostriatal system of weaver heterozygotes (wv/+). In normal cerebellum, Purkinje cells showed very high levels of hybridization signal for beta APP695, beta APP714 and beta APP751 RNA transcripts, and a moderate signal for the beta APP770 species. In weaver heterozygotes and homozygotes, Purkinje cells, which are typically not arranged in a monolayer, showed strong hybridization signal. No changes in beta APP mRNAs were observed in brain areas other than the cerebellum and ventral midbrain of weaver mutants. These findings suggest that the decreased beta APP gene expression seen in the cerebellum and SN of weaver mutants most likely represents an epiphenomenon of the regional nerve cell loss and, therefore, the wv gene defect on MMU 16 does not seem to influence the expression of the closely linked beta APP gene in brain areas outside the nigrostriatal pathway and cerebellar cortex.

Alternative Splicing↗
PubMed1996

Differential cellular pattern of gene expression for two distinct cGMP-inhibited cyclic nucleotide phosphodiesterases in developing and mature rat brain.

Cyclic GMP-inhibited phosphodiesterases are characterized by sensitivity of cAMP hydrolysis to inhibition by cGMP. This phosphodiesterase family contains at least two different isoforms (PDE3A and PDE3B) encoded by distinct genes and serving tissue-specific roles in regulation of lipolysis, glycogenolysis, myocardial contractility, and smooth muscle relaxation. Our previous work indicated an abundance of these two phosphodiesterase messenger RNAs in the embryonic rat brain, and therefore, to elucidate the potential functions of these enzymes in brain development as well as in mature brain function, the present study mapped cellular patterns of gene expression for these two enzymes from embryonic day 15 to adulthood using in situ hybridization histochemistry. Phosphodiesterase 3B isoform messenger RNA is uniformly expressed in germinal neuroepithelium and mature neurons, with distribution generally reflecting cell density. Phosphodiesterase isoform 3A messenger RNA, in contrast, demonstrates striking spatiotemporal specificity of expression, with three distinct patterns being evident. Firstly, this mRNA is highly abundant in both primary and secondary neuroepithelial germinal zones. Secondly, during early postnatal development PDE3A mRNA is transiently but highly expressed in neurons localized in basal forebrain, deep cerebellar, pontine, interpeduncular and a variety of thalamic, midbrain and brainstem nuclei. Thirdly, PDE3A mRNA is focally expressed in isolated large striatal and hippocampal neurons from the perinatal period without attenuation into adulthood. In summary, two cGMP-inhibited phosphodiesterase isoforms show distinctive patterns of gene expression in brain: PDE3B gene expression is uniform without evidence of system specificity or developmental stage specificity, suggesting that this isoform has a constitutive role in neuroepithelial metabolism, while PDE3B gene expression demonstrates a high level of spatiotemporal heterogeneity, suggesting that this isoform subserves a variety of developmental stage-specific and system-specific functions.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Sodium channel mRNAs I, II and III in the CNS: cell-specific expression.

The cellular localization of rat brain sodium channel alpha-subunit mRNAs I, II and III in the central nervous system (CNS) was examined by non-isotope in situ hybridization cytochemistry utilizing two independent sets of isoform-specific RNA probes, one set recognizing sodium channel isoforms in the coding region and the other in the non-coding region of the sodium channel messages. The independent sets of probes demonstrated qualitatively similar patterns of sodium channel mRNA expression. In the hippocampus, sodium channel mRNA I was very weakly expressed in the pyramidal layer and in the granular layer of the dentate gyrus; in contrast, sodium channel mRNA II was strongly expressed by neurons in these regions. Sodium channel mRNA III exhibited low-to-moderate expression in some neurons of the pyramidal layer of the hippocampus and granular layer of the dentate gyrus, and was not detectable in others. In the cerebellum, sodium channel mRNA I was moderately expressed in some Purkinje cells, weakly expressed in scattered cells in the molecular layer and negligibly expressed in the granular layer. Sodium channel mRNA II was strongly expressed in Purkinje and granule cells, and was moderately expressed in some cells in the molecular layer. Sodium channel mRNA III was generally not detectable in the cerebellum. In the spinal cord, motor neurons and scattered neurons throughout the gray matter exhibited moderate-to-strong expression of both sodium channel mRNA I and II. A population of cells in the spinal zone of Lissauer showed heavy expression of mRNA II, but not mRNA I. Sodium channel mRNA III was not detectable in spinal cord neurons. These observations are consistent with a general regional distribution of sodium channel message isoforms, with mRNA II being preferentially expressed in rostral regions of the CNS and mRNA I in caudal regions. However, the results also indicate that different cell types, within a given region, display different patterns of sodium channel mRNA expression. Moreover, these data suggest that individual neurons may express multiple forms of sodium channel mRNA.

Animals↗
PubMed1997

Cyclooxygenase 2 RNA message abundance, stability, and hypervariability in sporadic Alzheimer neocortex.

Long-term treatment by nonsteroidal anti-inflammatory drugs has been shown to decrease the incidence of Alzheimer's disease (AD). Both platelet-activating factor and interleukin-1beta, potent mediators of the inflammatory and immune response, strongly induce transcription of the cyclooxygenase-2 (COX-2) gene in brain cells. Using Northern and RT-PCR analysis, we have determined in 15 control and 10 sporadic AD human neocortical samples (age range, 60-82 yr; postmortem interval [PMI] range, 0.7-16.0 hr) the levels of COX-2 RNA in relation to the constitutively expressed COX-1 and beta-actin RNA message levels. Our results indicate that in short PMI brain, COX-1 and COX-2 transcripts are relatively low abundance RNA messages, ranging from a mean of 6.8% of the beta-actin signal in controls to 8.5% of the beta-actin signal in AD-affected brain. A large variation in the signal intensity for COX-2 RNA was noted in both control and AD; although there was a trend for higher COX-2 RNA message abundance in AD neocortex to +11.5% of that of controls, it did not reach statistical significance (ANOVA = 0.45). Several human tissues, including heart, skeletal muscle, lung, kidney, and spinal cord, displayed 4.6- and 2.8-kb COX-2 RNA message isoforms; however, the 4.6-kb COX-2 RNA predominated in the hippocampus and association neocortex. COX-2 RNA message was found to be degraded at similar rates in both control and AD tissues, and a strong positive correlation between the PMI and the intensity of the COX-2 RNA signal was noted (ANOVA = 0.006). Linear regression analysis indicated that the 4.6-kb COX-2 RNA is an unstable short-lived RNA species with a half-life of not more than 3.5 hr, a feature characteristic of immediate early gene transcripts. Individual hypervariability in COX-2 RNA message abundance may reflect various degrees of expression of AD-related inflammatory processes.

Aged↗
PubMed2002

Characterization and in vivo functional analysis of splice variants of cypher.

Previously, we reported two splice variants of Cypher, a striated muscle-specific PDZLIM domain protein, Cypher1 and Cypher2. We have now characterized four additional splice isoforms, two of which are novel. The six isoforms can be divided into skeletal or cardiac specific classes, based on the inclusion of skeletal or cardiac specific domains. Short and long isoforms share an N-terminal PDZ domain, but the three C-terminal LIM domains are unique to long isoforms. By RNA and protein analysis, we have demonstrated that Cypher isoforms are developmentally regulated in both skeletal and cardiac muscle. We have previously shown that knockout of Cypher is neonatal lethal. To investigate the function of splice variants in vivo, we have performed a rescue experiment of the Cypher null mutant by replacing the endogenous Cypher gene with cDNAs encoding either a short or long skeletal muscle isoform. In contrast to Cypher null mice, a percentage of mice that express only a short or a long skeletal muscle-specific isoform can survive to at least 1 year of age. Although surviving mice exhibit muscle pathology, these results suggest that either isoform is sufficient to rescue the lethality associated with the absence of Cypher.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Detection of neuron-specific gamma-enolase messenger ribonucleic acid in normal human leukocytes by polymerase chain reaction amplification with nested primers.

BACKGROUND: NNE (non-neuronal alpha-enolase) is a glycolytic enzyme detected in most tissues. NSE (neuron-specific gamma-enolase) is detected in normal neurons and tumors such as neuroblastoma. Staining with antibodies against NSE is therefore used to detect neuroblastoma cells invading bone marrow. Since staining of normal leukocytes has been reported we asked whether bona fide NSE is in fact expressed in normal blood and marrow. EXPERIMENTAL DESIGN: We designed nested coding region specific primers for NSE and NNE and, after reverse transcription of mRNA, we amplified the coding region between these primers in a semi-nested polymerase chain reaction. In order to distinguish both iso-mRNAs from each other, we amplified a long (1,047 bp) template in a first round of 30 cycles with primers specific for NNE or NSE. One percent of this product was used in a second round of 30 cycles in which both sense primers and two nested anti-sense primers of alternate specificities yielding shorter products of discernible sizes (768 bp or 619 bp) were added together in the same reaction tube. With this combination of four primers, only that shorter product was amplified to visibility, the specificity of which was homologous to the template produced in the first 30 cycles. Restriction enzyme digestion of the amplified products was used to verify this polymerase chain reaction-based approach for the distinction of isoforms of RNA. RESULTS: This semi-nested polymerase chain reaction clearly allows for the distinction of mRNA for NNE or NSE and shows the presence of transcripts for NSE in normal human leukocytes from blood and bone marrow. CONCLUSIONS: This method exploiting short stretches of nucleotide differences in the coding regions for priming can more generally be applied to the distinction of all isoforms of RNA where nested specific primers can be designed. However, the presence of NSE specific transcripts in normal human leukocytes invalidates the use of this highly sensitive method as a disease marker in neuroblastoma.

Base Sequence↗
PubMedDate not supplied

Prostate cancer overexpresses CD44 variants 7-9 at the messenger RNA and protein level.

BACKGROUND: In prostate cancer, prior data show down-regulated immunohistochemical expression of cell adhesion protein CD44 standard (CD44s) and most variants (CD44v). MATERIALS AND METHODS: Expression of CD44 mRNA was studied by RT-PCR and cDNA sequencing in 19 prostate cancers and 10 benign controls. Immunohistochemical staining was performed with anti-CD44v7/8 in 80 prostatectomy specimens, and 12 were used for in situ hybridization for CD44v7 (exon 12). Western blotting with monoclonal antibody to CD44 standard, v6, v7/8, or v9 was performed using cancerous and benign prostate. RESULTS: Sequencing of RT-PCR products showed that benign tissue and cancer express CD44 standard and v10 mRNA at 482 base pairs (bp). In contrast, cancer tissues also overexpressed 800-1000 bp bands corresponding to v7-9 isoforms. In situ hybridization revealed increased CD44v7 signal in cancer compared to benign acini. Immunostaining for CD44v7/8 was increased, proportional to Gleason grade. By Western blot, cancer and benign tissue disclosed major bands of reactivity at 75-100 kD consistent with intact standard and variant isoforms. Tumors, however, had 6-45 kD bands for CD44 standard, v7/8 and v9, consistent with cleavage products. CONCLUSION: CD44 v7-9 isoform messenger RNA is increased in prostate cancer, and translation yields low molecular weight polypeptides of probable cleavage origin.

Blotting, Western↗
PubMed2005

Implication of STAT3 signaling in human colonic cancer cells during intestinal trefoil factor 3 (TFF3) -- and vascular endothelial growth factor-mediated cellular invasion and tumor growth.

Signal transducer and activator of transcription (STAT) 3 is overexpressed or activated in most types of human tumors and has been classified as an oncogene. In the present study, we investigated the contribution of the STAT3s to the proinvasive activity of trefoil factors (TFF) and vascular endothelial growth factor (VEGF) in human colorectal cancer cells HCT8/S11 expressing VEGF receptors. Both intestinal trefoil peptide (TFF3) and VEGF, but not pS2 (TFF1), activate STAT3 signaling through Tyr(705) phosphorylation of both STAT3alpha and STAT3beta isoforms. Blockade of STAT3 signaling by STAT3beta, depletion of the STAT3alpha/beta isoforms by RNA interference, and pharmacologic inhibition of STAT3alpha/beta phosphorylation by cucurbitacin or STAT3 inhibitory peptide abrogates TFF- and VEGF-induced cellular invasion and reduces the growth of HCT8/S11 tumor xenografts in athymic mice. Differential gene expression analysis using DNA microarrays revealed that overexpression of STAT3beta down-regulates the VEGF receptors Flt-1, neuropilins 1 and 2, and the inhibitor of DNA binding/differentiation (Id-2) gene product involved in the neoplastic transformation. Taken together, our data suggest that TFF3 and the essential tumor angiogenesis regulator VEGF(165) exert potent proinvasive activity through STAT3 signaling in human colorectal cancer cells. We also validate new therapeutic strategies targeting STAT3 signaling by pharmacologic inhibitors and RNA interference for the treatment of colorectal cancer patients.

Apoptosis↗
PubMed2001

Identification of 66 box C/D snoRNAs in Arabidopsis thaliana: extensive gene duplications generated multiple isoforms predicting new ribosomal RNA 2'-O-methylation sites.

Dozens of box C/D small nucleolar RNAs (snoRNAs) have recently been found in eukaryotes (vertebrates, yeast), ancient eukaryotes (trypanosomes) and archae, that specifically target ribosomal RNA sites for 2'-O-ribose methylation. Although early biochemical data revealed that plant rRNAs are among the most highly ribomethylated in eukaryotes, only a handful of methylation guide snoRNAs have been characterized in this kingdom. We report 66 novel box C/D snoRNAs identified by computational screening of Arabidopsis genomic sequences that are expressed in vivo from either single genes, 17 different clusters or three introns. At the structural level, many box C/D snoRNAs have dual antisense elements often matching rRNA regions close to each other on the rRNA secondary structure, which is reminiscent of their archaeal counterparts. Remarkable specimens are found that display two antisense elements having the potential to form an extended snoRNA-rRNA duplex of 23 to 30 nt, in line with the hypothetical function of box C/D snoRNAs in pre-rRNA folding or chaperoning. In contrast to other species, many Arabidopsis snoRNAs are found in multiple isoforms mainly resulting from two different mechanisms: large chromosomal duplications and small tandem duplications producing polycistronic genes. The discovery of numerous different snoRNAs, some of them arising from common ancestors, provide new insights to understand snoRNAs evolution and the birth of new rRNA methylation sites in plants and other organisms.

Arabidopsis↗
PubMed2004

Synaptotagmin V and IX isoforms control Ca2+ -dependent insulin exocytosis.

Synaptotagmin (Syt) is involved in Ca2+ -regulated secretion and has been suggested to serve as a general Ca2+ sensor on the membrane of secretory vesicles in neuronal cells. Insulin exocytosis from the pancreatic beta-cell is an example of a Ca2+ -dependent secretory process. Previous studies have yielded conflicting results as to which Syt isoform is present on the secretory granules in the native beta-cell. Here we show by western blotting and RT-PCR analysis, the presence of both Syt V and Syt IX in rat pancreatic islets and in the clonal beta-cell line INS-1E. The subcellular distribution of the two Syt isoforms was assessed by confocal microscopy and by sedimentation in a continuous sucrose density gradient in INS-1E cells. These experiments show that both proteins colocalize with insulin-containing secretory granules but are absent from synaptic-like microvesicles. Further immunofluorescence studies performed in primary pancreatic endocrine cells revealed that Syt V is present in glucagon-secreting alpha-cells, whereas Syt IX is associated with insulin granules in beta-cells. Transient overexpression of Syt V and Syt IX did not alter exocytosis in INS-1E cells. Finally, reduction of the expression of both Syt isoforms by RNA interference did not change basal secretion. Remarkably, hormone release in response to glucose was selectively and strongly reduced, indicating that Syt V and Syt IX are directly involved in the Ca2+ -dependent stimulation of exocytosis.

Animals↗
PubMed2004

Two functionally redundant isoforms of Drosophila melanogaster eukaryotic initiation factor 4B are involved in cap-dependent translation, cell survival, and proliferation.

Eukaryotic initiation factor (eIF) 4B is part of the protein complex involved in the recognition and binding of mRNA to the ribosome. DrosophilaeIF4B is a single-copy gene that encodes two isoforms, termed eIF4B-L (52.2 kDa) and eIF4B-S (44.2 kDa), generated as a result of the alternative recognition of two polyadeynlation signals during transcription termination and subsequent alternative splicing of the two pre-mRNAs. Both eIF4B mRNAs and proteins are expressed during the entire embryogenesis and life cycle. The proteins are cytoplasmic with polarized distribution. The two isoforms bind RNA with the same affinity. eIF4B-L and eIF4B-S preferentially enhance cap-dependent over IRES-dependent translation initiation in a Drosophila cell-free translation system. RNA interference experiments suggest that eIF4B is required for cell survival, although only a modest reduction in rate of protein synthesis is observed. Overexpression of eIF4B in Drosophila cells in culture and in developing eye imaginal discs promotes cell proliferation.

Amino Acid Sequence↗
PubMed1999

The balance between two isoforms of the Drosophila RNA-binding protein how controls tendon cell differentiation.

In Drosophila, a tendon cell is selected from a group of equipotent precursors following its interaction with a muscle cell. This interaction results in elevated levels of the transcription factor Stripe in the future tendon cells. Here we show that the balance between two distinct forms of the RNA-binding protein How maintains low levels of Stripe at the precursor stage and high levels in the mature tendon. The long, nuclear-specific protein How(L) downregulates Stripe protein levels at the precursor stage by binding stripe mRNA and inhibiting its nuclear export. This inhibition is likely to be counteracted by the short How(S) protein, present in both nucleus and cytoplasm, which is upregulated in the muscle-bound tendon cell following EGF receptor activation.

Alternative Splicing↗
PubMed2006

CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver.

CD1d-restricted natural killer T (NKT) cells expressing invariant Valpha14Jalpha18 T cell receptor alpha-chains are abundant in murine liver and are implicated in the control of malignancy, infection and autoimmunity. Invariant NKT cells have potent anti-metastatic effects in mice and phase I clinical trials involving their homologues in humans are ongoing. However, invariant NKT cells are less abundant in human liver ( approximately 0.5% of hepatic T cells) than in murine liver (up to 50%) and it is not known if other hepatic T cells are CD1-restricted. We have examined expression of CD1a, CD1b, CD1c and CD1d mRNA and protein in human liver and evaluated the reactivity of mononuclear cells (MNC) from histologically normal and tumour-bearing human liver specimens against these CD1 isoforms. Messenger RNA for all CD1 isotypes was detectable in all liver samples. CD1c and CD1d were expressed at the protein level by hepatic MNC. CD1d, only, was detectable at the cell surface, but CD1c and CD1d were found at an intracellular location in significant numbers of liver MNC. CD1b was not expressed by MNC from healthy livers but was detectable within MNC in all tumour samples tested. Hepatic T cells exhibited reactivity against C1R cells expressing transfected CD1c and CD1d, but neither CD1a nor CD1b. These cells secreted interferon-gamma (IFN-gamma) but not interleukin-4 (IL-4) upon stimulation. In contrast, similar numbers of peripheral T cells released 13- and 16-fold less IFN-gamma in response to CD1c and CD1d, respectively. CD1c and CD1d expression and T cell reactivity were not altered in tumour-bearing liver specimens compared to histologically normal livers. These data suggest that, in addition to invariant CD1d-restricted NKT cells, autoreactive T cells that recognise CD1c and CD1d and release inflammatory cytokines are abundant in human liver.

Antigens, CD1↗