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At least 325 records · Page 18Linked to original sources
PubMed2001

Heterologous HIV-nef mRNA trans-splicing: a new principle how mammalian cells generate hybrid mRNA and protein molecules.

Heterologous trans-splicing is a messenger RNA (mRNA) processing mechanism, that joins RNA segments from separate transcripts to generate functional mRNA molecules. We present here for the first time experimental evidence that the proximal segment of the HIV-nef RNA segment can be trans-spliced to both viral (e.g. SV40 T-antigen) and cellular transcripts. Following either microinjection of in vitro synthesized HIV-nef and SV40 T-antigen pre-mRNA or transfection of the HIV-nef DNA into T-antigen positive cells (CV1-B3; Cos7), it was found that recipient cells synthesized HIV-nef/T-antigen hybrid mRNA and protein molecules. To generate the hybrid mRNA, the cells utilized the 5' cryptic splice sites of the HIV-nef (5'cry 66 and 5'cry 74) and the SV40 T/t-antigen 3' splice site. To demonstrate that heterologous trans-splicing also occurs between the HIV-nef RNA and cellular transcripts, a cDNA library was established from HIV-nef positive CV1-B3 cells (CV1-B3/13 cells) and screened for hybrid mRNA molecules. Reverse transcription-PCR and Northern blot analysis revealed that a significant portion of the HIV-nef transcript is involved in heterologous trans-splicing. To date, eight independent HIV-nef/cellular hybrid mRNA molecules have been identified. Five of these isolates contain segments from known cellular genes (KIAA1454, PTPkappa, Alu and transposon gene families), while three hybrid segments contain sequences of not yet known cellular genes (genes 1-3).

Animals↗
PubMed2002

Rat vasopressin mRNA: a model system to characterize cis-acting elements and trans-acting factors involved in dendritic mRNA sorting.

The genes encoding the vasopressin (VP) and oxytocin (OT) precursors are expressed in magnocellular neurons of the hypothalamo-neurohypophyseal system. The neuropeptides have a dual function: (1) they are secreted from the nerve terminals into the systemic circulation to act as hormones on various peripheral target organs; and (2) VP and OT are also released from the dendrites into the central nervous system where they presumably play a role as either neurotransmitters or as modulators of the classical transmitters. Substantial amounts of VP and OT mRNAs are sorted to both axons and dendrites. Since the latter are equipped with components of the translation machinery, the peptide hormone precursors are likely to be locally synthesized in dendrites of magnocellular neurons. Evidence for axonal precursor synthesis, on the other hand, has not been obtained. Subcellular mRNA localization is a complex pathway. It is determined by sequences (cis-acting elements) within the RNA and proteins (trans-acting factors) which interact with these elements in order to guide the molecules to their ultimate destination. We have investigated the mechanisms involved in mRNA targeting in neurons by using VP mRNA as a model system. Recombinant eukaryotic expression vectors harboring the VP cDNA have been microinjected into the cell nuclei of cultured superior cervical ganglion (SCG) neurons. The subcellular distribution of the vector-expressed mRNAs was determined by non-radioactive in situ hybridization techniques. This revealed transport of VP mRNA to the dendrites, but not to the axonal compartment of SCG neurons. A complex dendritic localizer sequence (DLS) that spans part of the coding region as well as the 3'-untranslated region was identified by microinjecting constructs encoding partial sequences of the VP mRNA. In order to characterize trans-acting factors interacting with this element, protein/RNA binding experiments with radiolabeled in vitro synthesized VP RNA probes and proteins extracted from rat brain have been carried out. A protein specifically interacts with the DLS of the VP mRNA but not with sequences that obviously lack a role in subcellular RNA transport. Biochemical purification revealed that this protein is the multifunctional poly(A)-binding protein (PABP). It is well known for its ability to bind with high affinity to poly(A) tails of mRNAs, prerequisite for mRNA stabilization and stimulation of translational initiation, respectively. With lower affinities, PABP can also associate with non-poly(A) sequences. The physiological consequences of these PABP/RNA interactions include functions such as translational silencing. The translational state of mRNAs subject to dendritic sorting is most likely influenced by external stimuli. Consequently, PABP could represent one of several components necessary to regulate local synthesis of the VP precursor and possibly of other proteins.

Animals↗
PubMed2000

Changes in estrogenic regulation of estrogen receptor alpha mRNA and progesterone receptor mRNA in the female rat hypothalamus during aging: an in situ hybridization study.

We examined two molecular responses to estrogen, reduction in estrogen receptor alpha (ER alpha) mRNA and increase in progesterone receptor (PR) mRNA, in the hypothalamus of 3- (young) and 10-month-old (middle-aged) cycling, and 15-month-old (old) acyclic, Fischer 344 female rats. The rats were ovariectomized and then given silastic capsules containing 5% 17beta-estradiol. or empty implants, and killed 4 days after implantation. By means of in situ hybridization, we found that, in young rats, estrogen reduced ER alpha mRNA in both the ventromedial hypothalamus (VMH) and arcuate nucleus (ARC) but not in the preoptic area (POA). In contrast, the effect of estrogen on ER alpha mRNA in the VMH and ARC of middle-aged and old rats was not statistically significant. On the other hand in all regions the induction of PR mRNA by estrogen was at least as strong in middle-aged and old as in young rats. The present study revealed that the induction of PR mRNA by estrogen in the hypothalamus was not impaired with age but ER alpha mRNA in the VMH and ARC was significantly impaired with age, but not in the POA.

Aging↗
PubMed1998

Highest trkB mRNA expression in the entorhinal cortex among hippocampal subregions in the adult rat: contrasting pattern with BDNF mRNA expression.

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, regulate synaptic functions in the hippocampus of the adult rodent. In previous studies, in situ hybridization methods have been used to evaluate regional differences in BDNF and trkB mRNA expression levels in hippocampal subregions. However, these studies have failed to reach consensus regarding the regional differences in the mRNA expression levels. In the present study, we quantitated mRNA expression levels using two different methods, ribonuclease protection assays and a quantitative reverse-transcription polymerase chain reaction technique, in four hippocampal subregions: the entorhinal cortex, dentate gyrus (DG), CA3 and CA1. These two methods yielded the same results. We found that BDNF and trkB mRNA expression levels did not covary in the four subregions. BDNF and full length trkB (trkB FL) mRNA in the entorhinal cortex and the DG show contrasting expression patterns. The expression level of BDNF mRNA was highest in the DG among the hippocampal subregions and low in the entorhinal cortex and the CA1, whereas the trkB FL mRNA expression level was highest in the entorhinal cortex, low in the DG and lowest in the CA3. These results suggest regional differences in BDNF/TrkB signaling for maintenance and modifiability of neuronal connections in the hippocampal formation.

Animals↗
PubMed1997

GAP-43 mRNA and calcitonin gene-related peptide mRNA expression in sensory neurons are increased following sympathectomy.

Sympathectomy has been shown to result in an increased density of fibers immunoreactive for sensory peptides in peripheral targets innervated by both sensory and sympathetic neurons, providing evidence for functional interactions between sympathetic and sensory systems. These findings provided the background for examining the hypothesis that axonal outgrowth is induced from sensory neurons following sympathectomy. We examined the expression of GAP-43 mRNA, a specific marker for axonal outgrowth, in cervical (C3, C7, C8) and thoracic (T1, T2) dorsal root ganglia (DRG) of the rat following bilateral removal of the superior cervical ganglion, to assess whether the described increases in peptidergic afferent fibers reflected axonal outgrowth. In situ hybridization was used with 35S labeled riboprobes complementary to GAP-43 mRNA, and to calcitonin gene-related peptide (CGRP) mRNA, a marker for a major subset of thin-fiber sensory neurons. The density of GAP-43 mRNA nearly doubled by 18 h following sympathectomy and reached a threefold increase by 3 days. By 45 days following surgery, the GAP-43 mRNA level was still nearly twice that of normal animals, CGRP immunoreactivity was also examined: the density of fibers in the iris and cornea of sympathectomized animals was considerably greater from two weeks to 45 days following surgery, than in sham-operated controls. Concomitantly, there was a slight but significant increase in CGRP mRNA expression in T1 and C3 DRG 14 days postsympathectomy. Quantitative computerized image analysis demonstrated that GAP 43 mRNA expression in sympathectomized animals was 1.5 times greater in medium-sized DRG neurons and almost fourfold greater in small DRG neurons than in control rats. These results indicate that sympathetic denervation elicits axonal outgrowth in the population of sensory neurons that give rise to the small unmyelinated and thinly myelinated axons of peripheral nerves.

Animals↗
PubMed2000

Characterization of NPY mRNA-expressing cells in the human brain: co-localization with Y2 but not Y1 mRNA in the cerebral cortex, hippocampus, amygdala, and striatum.

Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous system. Its effects on, for example, cognition, memory and motor functions are thought to be mediated mainly via its interactions with the NPY Y1 and Y2 receptor subtypes. We had previously described the neuroanatomical organization of the Y1 and Y2 mRNA expression in humans. However, in view of the lack of information regarding the overall detailed distribution of NPY mRNA expression in the human brain, a complete picture of the anatomical organization of the NPY-related genes was still missing. Thus, in the present study, the regional distribution of NPY mRNA-expressing cells was analyzed in the post-mortem human brain. In addition, double labeling in situ hybridization was performed to characterize the NPY neuronal populations in relation to the Y1 and/or Y2 receptor mRNA localization in the human cerebral cortex, striatum, and amygdala. NPY mRNA was found to be abundant in layers II and VI of the neocortex, polymorphic layer of the dentate gyrus, basal ganglia, and amygdala. Double labeling in situ hybridization showed the co-expression of NPY mRNA with the Y2, but not with the Y1, mRNA in the human cerebral cortex, hippocampus, amygdala, striatum, and nucleus accumbens, and the existence of co-expression of the Y1 and Y2 mRNAs in the cerebral cortex and amygdala. Overall, these results suggest a role for the Y2, but not Y1, as an autoreceptor in the NPY neuronal populations of the human brain.

Aged↗
PubMed2001

Expression of the mRNA (N6-adenosine)-methyltransferase S-adenosyl-L-methionine binding subunit mRNA in cultured cells.

Ribonuclease protection assays (RPA) were used to detect and quantitate the amount of messenger RNA (mRNA) coding for the S-adenosyl-L-methionine binding subunit (MT-A70) of the mRNA (N6-adenosine)-methyltransferase from different types of cultured cells. HeLa cells cultured in suspension were analyzed at regular intervals along a normal growth curve. It was discovered that MT-A70 mRNA was transcribed constitutively across the time-course, irrespective of the rate of cellular proliferation. Further, 11 different cell lines representing non-tumorigenic, tumorigenic, and virally-transformed tumorigenic types from Homo sapiens, Mus musculus, and Rattus norvegicus were examined for MT-A70 mRNA expression. It was found that all the cell lines expressed a long and short splice-variant form of the gene. In general, the cell lines expressed a similar total amount of the MT-A70 mRNA while statistically significant differences existed between the quantity of the long and short forms among cell types. Tumorigenic cell lines synthesized as much as a 9-fold greater amount of long form versus short form MT-A70 mRNA. Comparatively, non-tumorigenic cell lines generally expressed only a 1.5-fold greater amount of long form versus short form MT-A70 mRNA.

Animals↗
PubMed1994

mRNA binding track in the human 80S ribosome for mRNA analogues randomly substituted with 4-thiouridine residues.

The interaction between mRNA and 18S rRNA in human 80S ribosomes has been studied using synthetic mRNA analogues randomly substituted with 4-thiouridine, which can be photoactivated for cross-linking. Two mRNA analogues with different sequences have been used for complex formation with ribosomes without or with the presence of a cognate tRNA. Cross-linked 18S rRNA nucleotides were identified by reverse transcription analysis. The base U630 in 18S rRNA was the main target of cross-linking for both of the mRNA analogues studied, and three minor sites of cross-linking, A1060, U1046, and U966, were also identified. Thus, in the case of human 80S ribosomes, the set of nucleotide residues cross-linked to the mRNA analogues is significantly smaller than the twelve sites seen for Escherichia coli with these same two mRNA analogues [Bhangu, R., & Wollenzien, P. (1992) Biochemistry 31, 5937-5944]. The residue U630 is within a highly conserved region corresponding to the 530 loop region of eubacterial 16S rRNA; the cross-link to this site indicates that it plays a key role in interacting with mRNA on 80S ribosomes independently of the presence of a cognate tRNA at the P site.

Base Sequence↗
PubMed1997

TGF-beta 1 mRNA expression in clinical breast cancer and its relationship to ER mRNA expression.

Eighty nine primary breast cancers were investigated for the expression of TGF-beta 1 and ER mRNA using PCR of reverse transcribed RNA. PCR products were validated using Southern blots and hybridization with radiolabelled cDNA probes. TGF beta 1 mRNA was found to be expressed in 56/89 (63%) of the breast cancers while ER mRNA was expressed in 23/89 (26%) of the tumours. Using chi-square analysis TGF-beta mRNA expression was found to correlate significantly with ER mRNA expression (p < 0.001), in that virtually all tumours that expressed ER mRNA co-expressed TGF beta 1. In tumours that were ER mRNA negative, TGF beta 1 expression was more variable. These results suggest that during tumour progression, ER expression is lost more frequently than is growth factor expression.

Adult↗
PubMed1989

Feedback control of ornithine decarboxylase expression by polyamines. Analysis of ornithine decarboxylase mRNA distribution in polysome profiles and of translation of this mRNA in vitro.

Cell growth and differentiation require the presence of optimal concentrations of polyamines. Ornithine decarboxylase (ODC) catalyses the first and rate-controlling step in polyamine synthesis. In studies using cultures of Ehrlich ascites-tumour cells, we have shown that the expression of ODC is subject to feedback regulation by the polyamines. A decrease in the cellular polyamine concentration results in a compensatory increase in the synthesis of ODC, whereas an increase in polyamine concentration results in suppression of ODC synthesis. These changes in ODC synthesis were attributed to changes in the efficiency of ODC mRNA translation, because the steady-state amount of ODC mRNA remained constant. We now show that the number of ribosomes associated with ODC mRNA is low, and that the increase in ODC mRNA translation takes place without a shift in the distribution of ODC mRNA towards larger polysomes. This finding indicates that the polyamines regulate the efficiency of ODC mRNA translation by co-ordinately affecting the rates of initiation and elongation. By analysing ODC mRNA translation in vitro, using a rabbit reticulocyte lysate, polyadenylated RNA from a cell line with an amplified ODC gene, and a monospecific anti-ODC antibody, we also show that spermidine, but not putrescine, exerts a direct regulatory effect on ODC synthesis.

Animals↗
PubMed1996

Identification and characterization of a 44 kDa protein that binds specifically to the 3'-untranslated region of CYP2a5 mRNA: inducibility, subcellular distribution and possible role in mRNA stabilization.

Stabilization of mRNA is important in the regulation of CYP2a5 expression but the factors involved in the process are not known [Aida and Negishi (1991) Biochemistry 30, 8041-8045]. In this paper, we describe, for the first time, a protein that binds specifically to the 3'-untranslated region of CYP2a5 mRNA and which is inducible by pyrazole, a compound known to increase the half-life of CYP2a5 mRNA. We also demonstrate that pyrazole treatment causes an elongation of the CYP2a5 mRNA poly(A) tail, and that phenobarbital, which is transcriptional activator of the CYP2a5 gene that does not affect the mRNA half-life, neither induces the RNA-binding protein nor affects the poly(A) tail size. SDS/PAGE of the UV-cross-linked RNA-protein complex demonstrated that the RNA-binding protein has an apparent molecular mass of 44 kDa. The protein-binding site was localized to a 70-nucleotide region between bases 1585 and 1655. Treatment of cytoplasmic extracts with an SH-oxidizing agent, diamide, an SH-blocking agent, N-ethylmaleimide or potato acid phosphatase abolished complex-formation, suggesting that the CYP2a5 mRNA-binding protein is subject to post-translational regulation. Subcellular fractionation showed that the 44 kDa protein is present in polyribosomes and nuclei, and that its apparent induction is much stronger in polyribosomes than in nuclear extracts. We propose that this 44 kDa RNA-binding protein is involved in the stabilization of CYP2a5 mRNA by controlling the length of the poly(A) tail.

Animals↗
PubMed1980

Regulation of the stability of poly(I)xpoly(C)-induced human fibroblast interferon mRNA: selective inactivation of interferon mRNA and lack of involvement of 2',5'-oligo(A) synthetase activation during the shutoff of interferon production.

The inactivation of interferon mRNA during the shutoff phase of interferon production in poly(I)xpoly(C)-induced human fibroblast cultures is selective. We have determined that the shutoff of interferon production, which takes place from 3 to 8 hr after the beginning of induction, is not associated with an appreciable declined in the rate of bulk cellular protein synthesis or of cellular protein secretion. While the amount of translatable interferon mRNA declined markedly during the shutoff phase, the level of translatable bulk cellular mRNA and the stability of [3H]uridine-labeled mRNA were unaffected. Superinduction with actinomycin D selectively stabilized interferon mRNA with no apparent effect on the stability of bulk cellular mRNA. Furthermore, an activation of the 2',5'-oligo(A) synthetase/endonuclease system does not appear to be involved in the shutoff phenomenon. Uninduced FS-4 cells contained a low basal level of 2'5'-oligo(A) synthetase activity, which was unchanged in poly(I)xpoly(C)-induced cells during the shutoff phase. Treatment of FS-4 cells with interferon for 16-18 hr prior to induction increased the enzyme activity by approximately 200-fold. However, this did not inhibit interferon production after induction with poly(I)xpoly(C) alone or after superinduction with cycloheximide or actinomycin D or both. Furthermore, the rates of decay of interferon production were comparable in cells with either a basal or an increased level of 2',5'-oligo(A) synthetase. Thus a 200-fold increase in 2',5'-oligo(A) synthetase level did not affect either the stability of interferon mRNA or the efficacy of interferon superinduction by metabolic inhibitors.

2',5'-Oligoadenylate Synthetase↗
PubMed1998

Characterization of the rat Star gene that encodes the predominant 3.5-kilobase pair mRNA. ACTH stimulation of adrenal steroids in vivo precedes elevation of Star mRNA and protein.

The steroidogenic acute regulatory protein (STAR) participates in steroidogenesis through the mitochondrial transfer of cholesterol to cytochrome P450scc. The rat adrenal Star gene is transcribed as a 3. 5-kilobase pair (kb) and 1.6-kb mRNA with the larger mRNA predominating ( approximately 85% of total) in vivo. Hypophysectomy (HPX) produced a 3-5-fold decrease in Star mRNA along with a loss of adrenal steroids, whereas P450scc mRNA decreased by less than 2-fold. Adrenocorticotropic hormone (ACTH) treatment of HPX rats maximally stimulated steroidogenesis rates within 5 min with over 10-fold elevation of steady state blood levels occurring within 10 min. For intact rats there was a 5-10-fold larger increase, paralleling previously observed elevations of cholesterol-cytochrome P450scc association and metabolism in subsequently isolated adrenal mitochondria. ACTH did not increase either total STAR protein or a group of modified forms until at least 30 min after completion of acute stimulation, indicating that elevated translation of STAR protein cannot alone mediate this acute stimulation. Parallel slow changes in STAR protein and corticosterone formation after ACTH treatment are consistent with participation of STAR forms as co-regulators of these hormonal responses. ACTH stimulation of HPX rats increased Star mRNA by 2.5-fold within 20 min and by 4.5-fold after 1 h, thus preceding the rise in the STAR protein. A 3.5-kb Star cDNA clone isolated from a rat adrenal cDNA library exhibited a 0.9-kb open reading frame and a 2.5-kb 3'-untranslated region (3'-UTR). The open reading frame sequence differed at only 12 amino acids from that of the mouse Star. The rat Star gene seven exons with exon 7 encoding the entire 2.5 kb of 3'-UTR of the 3.5-kb mRNA. The 3'-UTR sequence suggests that 1.6- and 3.5-kb mRNA are formed by an alternative usage of different polyadenylation signals. Multiple UUAUUUA(U/A)(U/A) motifs also suggest additional regulation through this extended 3'-UTR. Although elevation of STAR protein by ACTH does not cause the acute increase in adrenal cholesterol metabolism, changes in the turnover or distribution of an active STAR subfraction cannot be excluded.

Adrenal Glands↗
PubMed2003

The mRNA-binding protein YB-1 (p50) prevents association of the eukaryotic initiation factor eIF4G with mRNA and inhibits protein synthesis at the initiation stage.

The cytoplasmic messenger ribonucleoprotein particles of mammalian somatic cells contain the protein YB-1, also called p50, as a major core component. YB-1 is multifunctional and involved in regulation of mRNA transcription and translation. Our previous studies demonstrated that YB-1 stimulates initiation of translation in vitro at a low YB-1/mRNA ratio, whereas an increase of YB-1 bound to mRNA resulted in inhibition of protein synthesis in vitro and in vivo. Here we show that YB-1-mediated translation inhibition in a rabbit reticulocyte cell-free system is followed by a decay of polysomes, which is not a result of mRNA degradation or its functional inactivation. The inhibition does not change the ribosome transit time, and therefore, it affects neither elongation nor termination of polypeptide chains and only occurs at the stage of initiation. YB-1 induces accumulation of mRNA in the form of free messenger ribonucleoprotein particles, i.e. it blocks mRNA association with the small ribosomal subunit. The accumulation is accompanied by eukaryotic initiation factor eIF4G dissociation from mRNA. The C-terminal domain of YB-1 is responsible for inhibition of translation as well as the disruption of mRNA interaction with eIF4G.

Animals↗
PubMed2004

An RNA-interacting protein, SYNCRIP (heterogeneous nuclear ribonuclear protein Q1/NSAP1) is a component of mRNA granule transported with inositol 1,4,5-trisphosphate receptor type 1 mRNA in neuronal dendrites.

mRNA transport and local translation in the neuronal dendrite is implicated in the induction of synaptic plasticity. Recently, we cloned an RNA-interacting protein, SYNCRIP (heterogeneous nuclear ribonuclear protein Q1/NSAP1), that is suggested to be important for the stabilization of mRNA. We report here that SYNCRIP is a component of mRNA granules in rat hippocampal neurons. SYNCRIP was mainly found at cell bodies, but punctate expression patterns in the proximal dendrite were also seen. Time-lapse analysis in living neurons revealed that the granules labeled with fluorescent protein-tagged SYNCRIP were transported bi-directionally within the dendrite at approximately 0.05 microm/s. Treatment of neurons with nocodazole significantly inhibited the movement of green fluorescent protein-SYNCRIP-positive granules, indicating that the transport of SYNCRIP-containing granules is dependent on microtubules. The distribution of SYNCRIP-containing granules overlapped with that of dendritic RNAs and elongation factor 1alpha. SYNCRIP was also found to be co-transported with green fluorescent protein-tagged human staufen1 and the 3'-untranslated region of inositol 1,4,5-trisphosphate receptor type 1 mRNA. These results suggest that SYNCRIP is transported within the dendrite as a component of mRNA granules and raise the possibility that mRNA turnover in mRNA granules and the regulation of local protein synthesis in neuronal dendrites may involve SYNCRIP.

3' Untranslated Regions↗
PubMed2005

A hairpin-like structure within an AU-rich mRNA-destabilizing element regulates trans-factor binding selectivity and mRNA decay kinetics.

In mammals, rapid mRNA turnover directed by AU-rich elements (AREs) is mediated by selective association of cellular ARE-binding proteins. These trans-acting factors display overlapping RNA substrate specificities and may act to either stabilize or destabilize targeted transcripts; however, the mechanistic features of AREs that promote preferential binding of one trans-factor over another are not well understood. Here, we describe a hairpin-like structure adopted by the ARE from tumor necrosis factor alpha (TNFalpha) mRNA that modulates its affinity for selected ARE-binding proteins. In particular, association of the mRNA-destabilizing factor p37(AUF1) was strongly inhibited by adoption of the higher order ARE structure, whereas binding of the inducible heat shock protein Hsp70 was less severely compromised. By contrast, association of the mRNA-stabilizing protein HuR was only minimally affected by changes in ARE folding. Consistent with the inverse relationship between p37(AUF1) binding affinity and the stability of ARE folding, mutations that stabilized the ARE hairpin also inhibited its ability to direct rapid mRNA turnover in transfected cells. Finally, phylogenetic analyses and structural modeling indicate that TNFalpha mRNA sequences flanking the ARE are highly conserved and may stabilize the hairpin fold in vivo. Taken together, these data suggest that local higher order structures involving AREs may function as potent regulators of mRNA turnover in mammalian cells by modulating trans-factor binding selectivity.

Base Sequence↗
PubMed1998

Presenilin-1 mRNA and beta-amyloid precursor protein mRNA are expressed in the developing rat olfactory and vestibulocochlear systems.

The mRNA expression of presenilin-1 (PS1) and beta-amyloid precursor protein (betaAPP) was investigated in the embryonic day 20 rat olfactory bulb, nasal cavity, and inner ear using in situ hybridization histochemistry. In the olfactory bulb, PS1 mRNA was strongly expressed in both olfactory bulb neuroepithelium and the differentiating olfactory bulb. In contrast, betaAPP mRNA was preferentially expressed in differentiating fields. In the nasal cavity, PS1 mRNA was strongly expressed throughout the olfactory epithelium, while betaAPP mRNA expression was concentrated in the middle part of the epithelium. In the membrane labyrinth of the inner ear, although PS1 mRNA was evenly distributed in both sensory epithelium and supporting cells, betaAPP mRNA was exclusively expressed in the sensory epithelium. These data suggest that PS1 is expressed earlier than betaAPP, and that PS1 and betaAPP co-operatively play pivotal roles in the development of the olfactory and vestibulocochlear systems.

Alzheimer Disease↗
PubMed1994

Cholestyramine and a fat-free diet lower apolipoprotein A-IV mRNA in jejunum and cholestyramine lowers apolipoprotein A-I mRNA in ileum of rats.

To investigate the effect of bile acids or dietary lipid on the expression of intestinal apolipoproteins, the mRNA levels of apolipoprotein A-I and A-IV in the intestine from rats fed a diet containing cholestyramine or a fat-free diet were compared with those from rats fed a control diet containing 25% casein and 5% corn oil. Plasma total cholesterol concentration was lower after 16 h in rats fed a diet containing cholestyramine or a fat-free diet than in rats fed a control diet. In rats fed the fat-free diet, HDL cholesterol concentration also was lower than in those fed the control diet. The pool of bile acid in intestinal contents was significantly lower in rats fed cholestyramine than in both other groups. The relative abundance of jejunal apolipoprotein A-I mRNA did not differ between groups. Jejunal apolipoprotein A-IV mRNA abundance was significantly lower than in controls in rats fed the fat-free and cholestyramine-containing diets. Abundance of apolipoprotein A-I mRNA in ileal mucosa was comparable to controls in rats fed a fat-free diet but was significantly lower in rats fed cholestyramine. Ileal apolipoprotein A-IV mRNA tended to be lower in rats fed cholestyramine and a fat-free diet than in controls. We propose that decreased absorption of dietary lipid may modulate changes in jejunal apolipoprotein A-IV mRNA level and low levels of bile acids in the lumen may modulate changes in ileal apolipoprotein A-I mRNA level.

Administration, Oral↗