SEARCH · PubMed Health

Results for “Protein Isoforms”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources

PubMed2004

Differential expression and antibacterial activity of epididymis protein 2 isoforms in the male reproductive tract of human and rhesus monkey (Macaca mulatta).

The epididymis protein 2 (EP2) gene, the fusion of two ancestral beta-defensin genes, is highly expressed in the epididymis and subject to species-specific regulation at the levels of promoter selection, transcription, and mRNA splicing. EP2 mRNA expression is also androgen dependent, and at least two of the secreted proteins bind spermatozoa. Alternative splicing produces more than 17 different EP2 mRNA variants. In this article, the expression of EP2 variants was profiled in different tissues from the human and rhesus monkey (Macaca mulatta) male reproductive tract using reverse transcriptase-polymerase chain reaction. Different EP2 mRNA variants were identified not only in human and rhesus testis and epididymis but also in the novel sites, seminal vesicle and prostate. Immunolocalization of EP2 protein in epithelial cells from rhesus and human seminal vesicle demonstrated that EP2 transcripts are translated in these tissues. In addition, two novel splicing variants, named EP2R and EP2S, were discovered. EP2C was the only splice variant expressed in all tissues tested from rhesus monkey. However, expression was not detected in human testis or seminal vesicle. For the first time, bactericidal function was demonstrated for EP2C, EP2K, and EP2L. Taken together, the results indicate that EP2 expression is more widespread in the male reproductive tract than realized previously. Whereas the activity of every EP2 variant tested thus far is antibacterial, further investigation may reveal additional physiological roles for EP2 peptides in the primate male reproductive tract.

Aged↗

PubMed1996

Differential regulation of histamine- and bradykinin-stimulated phospholipase C in adrenal chromaffin cells: evidence for involvement of different protein kinase C isoforms.

In this report we investigate the isoforms of protein kinase C (PKC) present in cultured adrenal chromaffin cells with respect to their modulation by treatment with phorbol ester and their possible differential involvement in the regulation of responses to histamine and bradykinin. The presence of individual isoforms of PKC was investigated by using eight isoform specific antisera, as a result of which PKC-alpha, epsilon, and zeta were identified. To characterize down-regulation of these enzymes, cells were incubated for 6-48 h with 1 microM phorbol myristate acetate (PMA). PKC-epsilon down-regulated more rapidly than PKC-alpha. At 12 h, PMA pretreatment, for example, PKC-epsilon was maximally down-regulated (23 +/- 4% of controls), whereas PKC-alpha was unchanged. PKC-alpha showed partial down-regulation by 24 h of PMA pretreatment. PKC-zeta did not down-regulate at any of the times tested. Translocation from cytosol to membrane in response to PMA was also more rapid for PKC-epsilon than for PKC-alpha. The accumulation of total 3H-inositol (poly) phosphates in response to bradykinin or histamine was essentially abolished by prior treatment with 10-min PMA treatment (1 microM). However, with 12-h exposure to PMA, the bradykinin response was restored to the level seen with no prior PMA exposure. The histamine response showed no recovery by 12 h of PMA, but showed partial recovery by 24 h of PMA pretreatment. These observations showed that the restoration of the response to bradykinin corresponds to the loss of PKC-epsilon, whereas the restoration of the histamine response corresponds to the loss of PKC-alpha. This picture was confirmed with further studies on cytosolic Ca2+. The results show that chromaffin cells exhibit an unusual pattern of down-regulation of PKC isoforms on prolonged exposure to PMA, and that there is a differential effect of exposure to PMA on the histamine and bradykinin responses, suggesting that different PLC-linked receptors in chromafin cells are differentially regulated by PKC isoforms.

Adrenal Glands↗

PubMed1995

Molecular characterization of the human transmembrane protein-tyrosine phosphatase delta. Evidence for tissue-specific expression of alternative human transmembrane protein-tyrosine phosphatase delta isoforms.

Protein-tyrosine phosphatases (PTPases) play an essential role in the regulation of cell activation, proliferation, and differentiation. A major subfamily of these enzymes is the transmembrane-type PTPases that contain extracellular regions comprised of Ig-like and fibronectin type III (FN-III)-like domains. Characterization of the human transmembrane PTPase delta (HPTP delta) revealed the existence of multiple HPTP delta isoforms that vary in their extracellular regions. The full-length HPTP delta isoform has an extracellular region containing three Ig-like and eight FN-III-like domains connected via a transmembrane peptide to an intracellular region with two PTPase domains, whereas another isoform lacks four of the eight FN-III like domains. Furthermore, other HPTP delta isoforms exist that lack 9 amino acids within the second Ig-like domain and 4 amino acids at the junction of the second and third Ig-like domains or 9 amino acids within the fifth FN-III-like domain. Reverse transcription polymerase chain reaction analysis demonstrated that HPTP delta isoforms lacking these short peptides are expressed in kidney, whereas isoforms containing these peptides are expressed in the brain. Analysis of HPTP delta biosynthesis demonstrated that HPTP delta is expressed as a complex of two noncovalently associated subunits derived from a proprotein and that the HPTP delta ectodomain is shed from the cell surface. Mutational analysis of the HPTP delta proprotein cleavage site revealed the existence of two or three functional and overlapping furin-like endoprotease cleavage sites.

Alternative Splicing↗

PubMed1992

Altered gene expression in fast-twitch muscle induced by chronic low-frequency stimulation.

Increased neuromuscular activity via chronic low-frequency stimulation induces multiple fast-to-slow transitions in phenotypic properties that ultimately lead to fiber type conversions in the fast-twitch muscle of small mammals. Most of these alterations occur in an ordered sequence and result from the sequentially altered expression of myofibrillar and other protein isoforms. These changes relate to altered levels of specific mRNAs, followed by alterations in protein synthesis. As shown by the exchange of myosin heavy chain isoforms, protein degradation may be an additional control factor involved in the rearrangement of the myofibrillar apparatus. The degree of the various fast-to-slow transitions is species dependent and may be related to differences in thyroid hormone levels. It is suggested that the drastically and persistently depressed phosphorylation potential of the ATP system possibly serves to trigger the transformation process.

Animals↗

PubMed2001

Dexamethasone, but not IL-1 alone, upregulates acute-phase serum amyloid A gene expression and production by cultured human aortic smooth muscle cells.

Although the SAA1 and SAA2 protein isoforms (A-SAA) of the serum amyloid A (SAA) family of acute phase reactants have been found in a number of extrahepatic tissues; the site of synthesis of extrahepatic SAA remains to be clarified. To investigate site(s) of synthesis of the SAA protein localized to atherosclerotic plaque, expression of the SAA1 and SAA2 genes by cultured human aortic smooth muscle cells (HASMC) was investigated. A-SAA protein isoforms were detectable by immunoblot analysis in the culture medium of HASMC. Both A-SAA and C-SAA (SAA4) mRNA isoforms were constitutively expressed by HASMC, but not, however, by the human umbilical vein endothelial cells. Expression of A-SAA mRNA by HASMC was upregulated by corticoid hormones including dexamethasone (Dex), corticosterone, hydrocortisone, and aldosterone, but not by the cytokines interleukin (IL)-1, IL-6, and tumour necrosis factor (TNF)-alpha alone. Dex stimulation of A-SAA mRNA was time and dose dependent from 6 to 48 h. The threshold concentration for upregulation of A-SAA mRNA in HASMC by Dex was between 0.1 and 1 nM. IL-1, known to upregulate extrahepatic A-SAA gene expression in other cell systems only slightly, if at all, upregulated Dex-induced A-SAA expression by HASMC. Thus, it is possible that some of the A-SAA protein in the vascular wall (atherosclerotic plaques) can originate from smooth muscle cells. In consideration of recent reports that A-SAA modulates the inflammatory process and lipid synthesis, A-SAA can potentially serve as a physiological regulator of smooth muscle cell homeostasis within that, in a disease state, participates in the formation of atherosclerotic plaques.

Acute-Phase Reaction↗

PubMed2006

Identification and characterization of recombinant and native rat myristoyl-CoA: protein N-myristoyltransferases.

Compared to other species that possess a single functional myristoyl-CoA: protein N-myristoyltransferase gene copy, human, mouse and cow possess 2 NMT genes, and more than 2 protein isoforms. In mammals, the contribution of each gene transcript to multiple protein isoform expression and enzyme activity remains unclear. In order to get new insight on their respective physiological role, we have cloned and characterized the two rat NMT cDNAs. Rat NMT1 and NMT2 cDNAs contain 1491 and 1590 nucleotides, respectively, with high identity with their mouse homologues. Polypeptide sequences exhibited 68.1% identity between NMT1 and 2. Recombinant rat NMT1 and 2 showed major immunoreactive forms at 66 and 50 kDa, although NMT2 is 33-amino acid longer than NMT1. Both proteins exhibited functional myristoyltransferase activity but NMT2 appeared to be 4-time less active than NMT1. Studies of native protein expression revealed that the level and sizes of NMT proteins greatly vary among rat tissues although NMT1 and 2 did not display tissue specific expression at the mRNA level. Altogether, these results suggest that NMT2 may contribute little to total NMT activity levels in vivo.

Acyl Coenzyme A↗

PubMed1998

Variation in the expression of the mRNA for protein kinase C isoforms in the rat suprachiasmatic nuclei, caudate putamen and cerebral cortex.

Using in situ hybridization, we have examined mRNA expression for five isoforms of protein kinase C (PKC alpha, beta1, beta2, gamma and epsilon) in the rat suprachiasmatic nuclei (SCN) and other central site during the 24 h cycle. The signal for each of these isoforms shows a marked local density within the SCN. In the absence of photic cues, there are changes in the expression of the mRNAs for the four isoforms that are Ca2+-dependent (alpha, beta1, beta2 and gamma), but not for one of the Ca2+-independent PKCs (epsilon). PKC alpha mRNA exhibits a monophasic rhythm of expression in the SCN with a peak at early subjective night, circadian time (CT) 14. In contrast, the mRNAs for PKC beta1, beta2 and gamma show a biphasic rhythm in the SCN with peaks at early subjective day, CT 0, and early subjective night, CT 14. The four Ca2+-dependent isoforms may therefore subserve phase-related functions within the SCN at the onset of subjective night and, in the case of beta1, beta2 and gamma, also at the onset of subjective day. Variation in the mRNAs for PKC beta1 and gamma (but not for alpha, beta2 or epsilon) is also found in the caudate putamen and in the cingulate and parietal cortex; the biphasic pattern of expression for these mRNAs is precisely in phase with that observed in the SCN. The beta1 and gamma isoforms may therefore contribute to temporally regulated functions at sites outside the SCN. The present observations raise the possibility that receptor-mediated regulation of circadian functions is modulated or even gated by circadian changes in intracellular components that participate in distinct signal cascades.

Animals↗

PubMed2001

Distinct and redundant roles of the two protein kinase A isoforms Tpk1p and Tpk2p in morphogenesis and growth of Candida albicans.

TPK1 and TPK2 encode both isoforms of protein kinase A (PKA) catalytic subunits in Candida albicans. Mutants lacking both TPK1 alleles showed defective hyphal morphogenesis on solid inducing media, whereas in liquid hypha, formation was affected slightly. In contrast, tpk2 mutants were only partially morphogenesis defective on solid media, whereas a strong block was observed in liquid. In addition, the yeast forms of tpk2-- but not tpk1-- mutants were completely deficient in invading agar. Because Tpk1p and Tpk2p differ in their N-terminal domains of approximately 80--90 amino acids, while the catalytic portions are highly homologous, the functions of hybrid Tpk proteins with exchanged N-terminal domains were tested. The results demonstrate that the catalytic portions mediate Tpk protein specificities with regard to filamentation, whereas agar invasion is mediated by the N-terminal domain of Tpk2p. Homozygous tpk1 and tpk2 mutants grew normally; however, a tpk2 mutant strain containing a single regulatable TPK1 allele (PCK1p-TPK1) at low expression levels was severely growth defective. It was completely blocked in hyphal morphogenesis and was stress resistant to high osmolarities or temperatures. Thus, both Tpk isoforms in C. albicans share growth functions but, unlike Saccharomyces cerevisiae isoforms, they have positive, specific roles in filament formation in different environments.

Alleles↗

PubMed1994

Differential regulation of protein kinase C isoforms in isolated neonatal and adult rat cardiomyocytes.

We have immunologically identified the isoforms of protein kinase C (PKC) present in neonatal and adult rat cardiomyocytes and examined their regulation by hormones and phorbol ester. Both cell types express the Ca(2+)-dependent alpha-PKC and the Ca(2+)-independent epsilon- and delta-PKC isoforms. The atypical zeta-PKC isoform is also expressed in neonatal, but only weakly in adult cells. Stimulation of the alpha 1-adrenergic or purinergic receptor with phenylephrine or ATP, respectively, increases membrane-associated immunoreactivity of both epsilon- and delta-PKC in neonatal and adult cells; endothelin and carbachol are also effective in adult cells. In contrast, none of the agonists leads to increases in membrane-associated alpha-PKC in cardiomyocytes. PKC zeta is also unaffected by receptor stimulation. The phorbol ester phorbol 12-myristate 13-acetate causes redistribution and subsequently down-regulation of alpha-, epsilon-, and delta- but not zeta-PKC. The three isoforms are down-regulated at distinctively different rates, with alpha-PKC being the most rapid and epsilon-PKC the slowest. We used selective down-regulation of alpha-, epsilon-, and delta-PKC to investigate the role of these isoforms in PKC phosphorylation-dependent events in neonatal myocytes. Our findings suggest that epsilon-PKC is responsible for the phenylephrine-induced phosphorylation of MARCKS, an endogenous PKC-specific substrate. In contrast, agonist-induced c-fos expression is unlikely to be mediated by epsilon-PKC since the response is rapidly down-regulated and apparently Ca(2+)-dependent. Our finding that the PKC isoforms are differentially responsive to neurohormones suggests that they play distinct and specific roles in cardiac function.

Aging↗

PubMed1997

Spatial memory is related to hippocampal subcellular concentrations of calcium-dependent protein kinase C isoforms in young and aged rats.

Relationships were examined between spatial learning and hippocampal concentrations of the alpha, beta2, and gamma isoforms of protein kinase C (PKC), an enzyme implicated in neuronal plasticity and memory formation. Concentrations of PKC were determined for individual 6-month-old (n = 13) and 24-month-old (n = 27) male Long-Evans rats trained in the water maze on a standard place-learning task and a transfer task designed for rapid acquisition. The results showed significant relationships between spatial learning and the amount of PKC among individual subjects, and those relationships differed according to age, isoform, and subcellular fraction. Among 6-month-old rats, those with the best spatial memory were those with the highest concentrations of PKCgamma in the particulate fraction and of PKCbeta2 in the soluble fraction. Aged rats had increased hippocampal PKCgamma concentrations in both subcellular fractions in comparison with young rats, and memory impairment was correlated with higher PKCgamma concentrations in the soluble fraction. No age difference or correlations with behavior were found for concentrations of PKCgamma in a comparison structure, the neostriatum, or for PKCalpha in the hippocampus. Relationships between spatial learning and hippocampal concentrations of calcium-dependent PKC are isoform-specific. Moreover, age-related spatial memory impairment is associated with altered subcellular concentrations of PKCgamma and may be indicative of deficient signal transduction and neuronal plasticity in the hippocampal formation.

Aging↗

PubMed1997

Immunostaining with antibodies against protein kinase C isoforms in the fovea of the monkey retina.

We reported previously that an antibody to the alpha isoform of protein kinase C (PKC) immunostained rod bipolar cells and bipolar cells that could be blue-cone (B-cone)-specific in postmortem human retina (Kolb et al. (1993) Vis. Neurosci. 10:341-351). In addition, we showed that antibodies to the beta isoform of PKC immunostained cone system bipolar, amacrine, and ganglion cells. Since the fixation of the human material was poor, we were unable to make positive identifications of the specific cell types that were immunoreactive, particularly in the case of PKC-beta antibodies. Thus, herein we have repeated the study on well-fixed monkey foveal retina. PKC-alpha immunoreactivity (IR) was restricted to a single type of cone bipolar cell that contacted only a minority of the cone pedicles at central invaginating contacts of ribbon triads. This bipolar type shares some morphological characteristics of B-cone-specific bipolar cells of primate retina. PKC-beta immunoreactivity was found in cone bipolar cells that made primarily basal contacts with cone pedicles and had axon terminals in sublamina alpha of the inner plexiform layer (IPL). Immunoreactivity also occurred in a type of cone bipolar that made central element contacts and had axon terminals in sublamina b of the IPL. Some ganglion cells, particularly those postsynaptic to flat midget bipolar cells also exhibited PKC-beta-IR. One type of amacrine with an 8 microns diameter cell body showed strong PKC-beta-IR. It was postsynaptic to cone bipolar cells in both sublamina a and b and presynaptic to bipolar axons, other immunoreactive amacrine cells, and ganglion cell dendrites and bodies. The other amacrine cell type showed less strong PKC-beta-IR, large-bodied (12-15 microns cell body diameter), and probably diffuse in branching pattern. The latter interacted with the intensely immunoreactive amacrines, bipolars, and ganglion cells. By comparison to cat and primate retinas where morphology and physiology of many retinal neurons are well documented, we suggest that PKC-beta may be specific to flat midget, flat diffuse, and invaginating diffuse cone bipolar cells and to at least two amacrine cells. Some of these neural types are proposed to be involved in OFF-center cone pathways in the monkey retina.

Animals↗

PubMed2000

Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform.

Munc13 proteins constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3). With the exception of a ubiquitously expressed Munc13-2 splice variant, Munc13 proteins are brain-specific. Munc13-1 has a central priming function in synaptic vesicle exocytosis from glutamatergic synapses. In order to identify Munc13-like proteins that may regulate secretory processes in non-glutamatergic neurons or non-neuronal cells, we developed protein profiles for two Munc13-homology-domains (MHDs). MHDs are present in a wide variety of proteins, some of which have previously been implicated in membrane trafficking reactions. Taking advantage of partial sequences in the human expressed sequence tag (EST) database, we characterized a novel, ubiquitously expressed, rat protein (Munc13-4) that belongs to a subfamily of Munc13-like molecules, in which the typical Munc13-like domain structure is conserved. Munc13-4 is predominantly expressed in lung where it is localized to goblet cells of the bronchial epithelium and to alveolar type II cells, both of which are cell types with secretory function. In the present study we identify a group of novel proteins, some of which may function in a Munc13-like manner to regulate membrane trafficking. The MHD profiles described in the present study are useful tools for the identification of Munc13-like proteins, that would otherwise have remained undetected.

Alternative Splicing↗

PubMedDate not supplied

Distribution of protein kinase C isoforms in the cat retina.

Immunocytochemical localization was carried out for five isoforms of protein kinase C (PKC) in the cat retina. In common with other mammalian species, PKCalpha was found in rod bipolar cells. Staining was also seen in a small population of cone bipolar cells with axon terminals ramifying near the middle of the inner plexiform layer (IPL). PKCbetaI was localized to rod bipolar cells, one class of cone bipolar cell, and numerous amacrine and displaced amacrine cells. Staining for PKCbetaI was seen in three types of cone bipolar cells as well as in amacrine and ganglion cells. Immunoreactivity for both PKCepsilon and PKCzeta was found in rod bipolar cells; PKCepsilon was also seen in a population of cone bipolar cells and a few amacrine and ganglion cells whereas PKCzeta was found in all ganglion cells. Double-label immunofluorescence studies showed that dendrites of the two PKCbetaII-positive OFF-cone bipolar cells exhibit immmunoreactivity for the kainate-selective glutamate receptor GluR5. The third PKCbetaII cone bipolar is an ON-type cell and did not stain for GluR5. The retinal distribution of these isoforms of PKC is consistent with a role in modulation of various aspects of neurotransmission including synaptic vesicle release and regulation of receptor molecules.

Animals↗

PubMed2001

Characterisation of cAMP-dependent protein kinase isoforms in the brain of the crab Chasmagnathus.

In the crab Chasmagnathus learning model, systemic administration of cAMP analogues that are specific activators or inhibitors of cAMP-dependent protein kinase (PKA) proved to respectively facilitate or impair long-term retention. The aims of the present work were to analyse PKA activity distribution in the crab brain and to characterise PKA isoforms. The neuropils from the eyestalk showed higher levels of induced PKA activity when compared with other neuropils of the central nervous system. Two PKA isoforms, homologous to mammalian PKA I and PKA II, were detected from central brain protein extracts using DEAE chromatography. Only PKA II was found in lateral protocerebrum extracts, suggesting a role of this isoform in the processing of visual inputs and in the integration of this information with other sensory inputs. PKA I was observed to be ten-fold more sensitive to cAMP than PKA II. cGMP induced a high activation of both PKA isoforms, similar to that obtained with cAMP. PKA I showed a two-fold greater sensitivity for cGMP than PKA II. An autophosphorylation assay was performed and a protein of 55 kDa, corresponding to phosphorylated R II regulatory subunit, was detected. The presence of a PKA I isoform with high sensitivity for cAMP in the central brain suggests a role of this subtype in long-term memory.

Animals↗

PubMed2002

Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles.

The effects of endurance training on the response of muscle AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) to moderate treadmill exercise were examined. In red quadriceps, there was a large activation of alpha 2-AMPK and inactivation of ACC in response to exercise. This response was greatly reduced after training, probably because of reduced metabolic stress. In white quadriceps, there were no effects of exercise on AMPK or ACC, but alpha 2-activity was higher after training because of increased phosphorylation of Thr(172). In soleus, there were small increases in alpha 2-activity during exercise that were not affected by training. The expression of all seven AMPK subunit isoforms was also examined. The beta 2- and gamma 2-isoforms were most highly expressed in white quadriceps, and gamma 3 was expressed in red quadriceps and soleus. There was a threefold increase in expression of gamma 3 after training in red quadriceps only. Our results suggest that gamma 3 might have a special role in the adaptation to endurance exercise in muscles utilizing oxidative metabolism.

AMP-Activated Protein Kinases↗

PubMed2006

Expression of protein kinase C isoforms in cardiac hypertrophy and heart failure due to volume overload.

The present study determined whether changes in the activity and isoforms of protein kinase C (PKC) are associated with cardiac hypertrophy and heart failure owing to volume overload induced by aortocaval shunt (AVS) in rats. A significant increase in Ca2+-dependent and Ca2+-independent PKC activities in the homogenate and particulate fractions, unlike the cystolic fraction, of the hypertrophied left ventricle (LV) were evident at 2 and 4 weeks after inducing the AVS. This increase coincided with increases in PKC-alpha and PKC-zeta contents at 2 week and increases in PKC-alpha, PKC-beta1, PKC-beta2, and PKC-zeta contents at 4 weeks in the hypertrophied LV. By 8 and 16 weeks of AVS, PKC activity and content were unchanged in the failing LV. On the other hand, no increase in the PKC activity or isoform content in the hypertrophied right ventricle (RV) was observed during the 16 weeks of AVS. The content of G alpha q was increased in the LV at 2 weeks but then decreased at 16 weeks, whereas G alpha q content was increased in RV at 2 and 4 weeks. Our data suggest that an increase in PKC isoform content neither plays an important role during the development of cardiac hypertrophy nor participates in the phase leading to heart failure owing to volume overload.

Animals↗

PubMed1997

Expression of human myometrial G alpha s messenger ribonucleic acid transcript during pregnancy and labour: involvement of alternative splicing pathways.

We have shown previously that expression of 46 and 54 kDa human myometrial G alpha s protein isoforms is increased during gestation and then subsequently decreased during labour. These proteins appear to be coded for by G alpha s-Small (with a serine residue at position 72) and G alpha s-Large (with a serine residue at position 87) mRNA splice variants respectively. In the study presented here we have used a G alpha s cDNA template to generate [32P]cytidine cRNA riboprobes for use in RNase protection assays, so as to measure total myometrial G alpha s mRNA levels in relation to the pattern of expression of G alpha s mRNA splice variants during pregnancy and labour. We report that total levels of human myometrial G alpha s mRNA remain similar in non-pregnant and pregnant women but are substantially reduced during parturition. Our data also provide strong evidence that alternative splicing of G alpha s precursor mRNA has a primary role in regulating expression of G alpha s protein isoforms during pregnancy and labour. The inclusion of an additional serine codon in G alpha s mRNAs during pregnancy involves a switch in alternative splicing pathways. We speculate that this switch may be due to a change in specificity of splicing factors that are modulated during pregnancy and labour.

Adult↗

PubMed1993

Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform.

To investigate the molecular basis of prion diversity, we inoculated transgenic mice expressing the Syrian hamster prion protein (PrP) with three distinct prion isolates. We compared the three isolates designated Sc237, 139H, and Me7H in Tg(SHaPrP)7 mice with clinical signs of scrapie because the incubation times with these mice are considerably shorter than the times found with hamsters. Each prion isolate produced a distinctive pattern of the scrapie isoform of PrP (PrPSc) accumulation, as determined by histoblotting, a technique developed for the regional mapping of PrPSc deposition. The PrPSc pattern with the Me7H isolate was particularly interesting because it appeared to be confined to the hypothalamus and related structures--including the interstitial nucleus of the stria terminalis, the paraventricular nucleus of the thalamus, and periaqueductal grey. Additionally, the regions of PrPSc accumulation remained highly restricted, even though the incubation time for Me7H scrapie was significantly longer than with Sc237 and 139H isolates. Neuropathological changes characterized by neuronal vacuolation and astrocytic gliosis were confined to those regions where PrPSc accumulated. These findings argue that the cell-specific propagation of prion isolates may be responsible for different properties exhibited by each of the isolates.

Animals↗