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PubMed1986

Actin isoform synthesis and mRNA levels in quiescent and proliferating rat aortic smooth muscle cells in vivo and in vitro.

The relative levels of actin isoform synthesis in rat aortic smooth muscle cells (SMC) have been studied in vivo and in culture by means of [35S]methionine incorporation. They have been compared to the functional levels of actin isoform mRNAs, assayed by translation of total cell RNA in a reticulocyte lysate or, in some cases, to the actin isoform RNA content, assayed by Northern-blot hybridization to a total actin cRNA probe. In normal media and in freshly isolated SMC, the relative levels of actin isoform synthesis and the actin mRNA translation products show a remarkable similarity, but differ from the proportions of actin isoforms present in a total cell extract (Gabbiani G, Kocher O, Bloom WS, Vandekerckhove J, Weber K: Actin expression in smooth muscle cells of rat aortic intimal thickening, human atheromatous plaque, and cultured rat aortic media. J Clin Invest 73:148, 1984); (Skalli O, Bloom WS, Ropraz P, Azzarone B, Gabbiani G: Cytoskeletal remodeling of rat aortic smooth muscle cells in vitro: relationship to culture conditions and analogies to in vivo situations. J Submicrosc Cytol, in press 1986). This suggests that different actin isoforms have different stabilities. Fifteen days after balloon induced endothelial denudation in vivo, and after being placed in culture, SMC show a decrease in the proportions of alpha-actin synthesis and alpha-actin mRNA levels with a corresponding increase in these parameters for beta- and lambda-actins. The proportions of actin isoform synthesis and actin mRNA translation products in intimal SMC revert to normal values 60 days after balloon induced endothelial denudation, when the aorta is reendothelialized; however, in culture decreased alpha-actin synthesis and mRNA level persist up to the fifth passage (P5). These changes may be helpful for the understanding of SMC adaptation mechanisms during arterial development and atheromatous plaque formation.

Actins↗
PubMed1995

Developmental and regional expression of multifunctional Ca2+/calmodulin-dependent protein kinase isoforms in rat brain.

Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) participates in diverse calcium signaling pathways in neurons. The alpha- and beta-CaM kinase isoforms are neuron-specific and highly abundant in rat brain. The variable domain of CaM kinase is a potential site for the generation of isoform diversity by alternative spicing of its N- and/or C-terminal segments. We used specific PCR primers which span the variable domain of either alpha- or beta-CaM kinase and isolated three new isoforms from rat brain, namely alpha B-, beta e- and beta'e-CaM kinase. alpha beta-CaM kinase contains 11 amino acids, likely inserted by alternative splicing, at the C-terminal segment of the variable domain. This insertion introduces a nuclear localization signal (NLS) that targets alpha B-CaM kinase to the nucleus of transfected cells; alpha-CaM kinase is excluded from the nucleus. The mRNA and the protein corresponding to this isoform are detected only in the diencephalon/midbrain regions. We have also identified two alternatively spliced isoforms of beta-CaM kinase that lack the 24 amino acid sequence at the N-terminal segment of the variable domain. Alternative splicing of these two isoforms occurs with a three base pair shift of the 3'-splice site. Our analysis shows that these new beta-CaM kinase isoforms are expressed primarily in early developmental stages, and we therefore term them beta e - (embryonic) and beta' e-CaM kinase. Recombinant alpha B-, beta e and beta' e-CaM kinase expressed in COS-7 cells exhibit characteristic Ca2+/calmodulin-dependent protein kinase activity and autophosphorylation.

Aging↗
PubMed1993

Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia.

Because mutations in receptor tyrosine kinases may contribute to cellular transformation, studies were undertaken to examine c-kit in human leukemia. Isoforms of c-kit have been characterized in the human megakaryoblastic leukemia cell line M-07. Deletion of the four amino acids Gly-Asn-Asn-Lys in the extracellular domain represents an alternatively spliced isoform that has been shown by others, in mice, to be associated with constitutive receptor autophosphorylation (Reith et al, EMBO J 10:2451, 1991). Additional isoforms differ in the inclusion or exclusion of a serine residue in the interkinase domain, a region that contains the binding site for phosphatidylinositol 3-kinase. By RNase protection analysis, we have shown coexpression of the Gly-Asn-Asn-Lys+ and Gly-Asn-Asn-Lys- isoforms, with dominance of the Gly-Asn-Asn-Lys- transcript, in normal human bone marrow, normal melanocytes, a range of tumor cell lines, and the blasts of 23 patients with acute myeloid leukemia. Analysis of transcripts for the Ser+ and Ser- isoforms also showed coexpression in all normal and leukemic cells examined. The ratios of isoform expression for both the Gly-Asn-Asn-Lys and Ser variants were relatively constant, providing no evidence in the tumors examined that upregulation of one isoform contributes to the neoplastic process.

Amino Acid Sequence↗
PubMed1995

ErbB-3 mediates differential mitogenic effects of NDF/heregulin isoforms on mouse keratinocytes.

The family of Neu differentiation factors (NDFs, or heregulins) includes a dozen secreted glycoproteins, whose receptor binding domain displays two variants, alpha and beta, and they bind to two receptor tyrosine kinases, ErbB-3 and ErbB-4. Certain isoforms were reported to induce growth-arrest and differentiation of mammary tumor cells, while other breast cancer cell lines responded mitogenically. The present study addressed the biologic effects of various NDF isoforms on normal EGF-dependent epithelial cells, Balb/MK keratinocytes, that can undergo either proliferation or differentiation. We found that beta isoforms of NDF induced a mitogenic effect, that was significantly smaller than the maximal response to EGF. By contrast with NDF-beta, NDF-alpha isoforms exerted almost no mitogenic effect, but they were sufficient to maintain keratinocytes in culture. Consistent with their higher mitogenic potency, NDF-beta isoforms bound to Balb/MK cells with higher affinity (Kd = 2.2 nM) than alpha isoforms, however both groups shared their receptor, that we identified as ErbB-3. No transcript of ErbB-4 was detectable in the keratinocytes, but these cells express multiple NDF mRNAs and also ErbB-2. We conclude that different isoforms of NDF induce distinct growth regulatory effects on cultured keratinocytes, through direct interaction with ErbB-3.

Animals↗
PubMed1995

Novel isoforms of murine intercellular adhesion molecule-1 generated by alternative RNA splicing.

Intercellular adhesion molecule-1 (ICAM-1)-deficient mice, produced by homologous recombination and previously recognized to be devoid of the common form of ICAM-1, are shown to express residual amounts of ICAM-1 Ag in thymus and lung. We demonstrate that this expression of ICAM-1 is possible because the mutated exon 5 in these animals has been skipped by alternative splicing of RNA. Three different alternative isoforms of ICAM-1 are expressed in mutant mice. Moreover, two of these isoforms are expressed in wild-type mice together with two additional alternative isoforms that cannot be produced in mutant mice. All alternatively spliced isoforms of ICAM-1 detected are missing complete extracellular Ig domains. In both mutant and wild-type mice, expression of alternatively spliced isoforms is up-regulated following stimulation of animals with LPS. Furthermore, all alternative isoforms of ICAM-1, except one, retain the ability to bind to the well-recognized ICAM-1 counter-receptor LFA-1. These findings, along with the restricted tissue distribution in mutant mice, indicate that alternative isoforms of ICAM-1 are significant physiologic adhesion structures which could play a distinct role in the functioning of the immune system of intact animals.

Alternative Splicing↗
PubMed1995

[Production of specific antibodies against isoforms of the beta subunit of human Na,K-ATPase].

The study of the differential and functional tissular distribution of the isoforms of Na,K-ATPase, an enzyme located on the plasma membrane of animal cells, must be performed with the aid of antibodies capable of specifically recognising beta 1 and beta 2 subunits. In order to facilitate the study of the functions and distribution of such isoforms, proteins were generated using pET series plasmid construction and transformation in E coli bacteria, and their production was promoted with IPTG, these being the antigens that induce antibodies specific for each isoform. The antisera thus obtained were used in Western Blot assays with tissue microsomes from different animal species; specifically, beta 1 and beta 2 isoforms of Na,K-ATPase could be recognised. A panel of polyclonal antibodies was obtained which proved capable of recognising these isoforms in different animal species, as well as their deglycosylated isoform. Such antibodies can be used as an efficient tool for functional and tissue distribution studies of the two isoforms.

Antibody Formation↗
PubMed1994

Immunocytochemical detection of the specific association of different PIC isoforms with cytoskeletal and nuclear matrix compartments in PC12 cells.

The increasing evidence of discrete roles of phosphoinositidase C (PIC) isoforms and the assessment of their localization in the cytoskeleton and in the nucleus support the involvement of particular isotypes of this enzyme in signal transduction at multiple levels. PC12 rat pheochromocytoma is one of the few cell lines expressing three immunologically distinct isoforms of PIC. We have analyzed the subcellular distribution of the PIC beta 1, gamma 1 and delta 1 isoforms using confocal and electron microscope immunocytochemistry. PIC beta 1 is mainly found in the nucleus and is associated with interchromatin domains. On the other hand, the PIC gamma 1 isoform is found in the nucleus and in the cytosol, while PIC delta 1 is exclusively cytoplasmic. Immunoblot and immunocytochemical experiments indicate that the various PIC isoforms are differently bound to structural cell compartments, such as cytoskeletal and nuclear matrix elements. In fact, PIC beta 1 and PIC gamma 1 isoforms are tightly associated with the nuclear matrix, while only about 50% of PIC gamma 1 is associated with the cytoskeleton after DNase I and high salt extractions. PIC gamma 1 is almost completely soluble under these conditions. These results further confirm the complexity of the inositide signal transduction mechanism, which involves several PIC isoforms, specifically localized in different cell compartments and support the existence of a membrane-unrelated inositol lipid-dependent signalling in the nuclear interior.

Animals↗
PubMed1994

Functional characterization of three isoforms of the Na+/H+ exchanger stably expressed in Chinese hamster ovary cells. ATP dependence, osmotic sensitivity, and role in cell proliferation.

Four distinct isoforms of the mammalian Na+/H+ exchanger (NHE) have been identified by molecular cloning. Three of these (NHE-1, NHE-2, and NHE-3) have been shown to be functionally active by heterologous expression. Their kinetic and pharmacological properties are well documented, yet comparatively little is known about their regulation. In this report, rat NHE-1, NHE-2, and NHE-3 were stably transfected into antiporter-deficient Chinese hamster ovary cells to study their role in cellular proliferation and their regulation by nucleotides and cell volume. Their ability to influence cell proliferation was assessed by measuring the growth of antiporter-deficient cells and of the different transfectants in media of varying pH. While antiporter-deficient cells were unable to grow at acidic pH levels, all three isoforms supported proliferation under these conditions. Therefore, while the epithelia-specific isoforms (NHE-2 and NHE-3) are thought to play primarily a role in transcellular ion transport, they can also contribute to intracellular pH (pHi) homeostasis and have a permissive role in cell growth. The activity of the three isoforms was markedly inhibited by depletion of cellular ATP. In the pHi 6.0-7.2 range, decreases in the affinity for internal H+ and/or the maximal rate of transport accounted for the inhibitory effect, depending on the isoform. The osmotic responsiveness of the three isoforms was also compared. As reported earlier, NHE-1 was stimulated by hypertonicity. Under similar conditions, NHE-2 was also stimulated to a comparable extent. Conversely, both isoforms were inhibited in hypotonic media. In contrast, NHE-3 was markedly inhibited by hypertonic cell shrinking but was unaffected by hypotonicity. Osmotic inhibition of NHE-3 was rapid, reversible, and apparent throughout the pH range studied. Osmotic inhibition of NHE-3 may play a role in the physiology and pathophysiology of epithelia.

Adenosine Triphosphate↗
PubMed1994

Alpha, beta I, beta II, delta, and epsilon protein kinase C isoforms and compound activity in the sciatic nerve of normal and diabetic rats.

Defective protein kinase C (PKC) has been implicated in impaired Na+,K(+)-ATPase activity in the sciatic nerve of streptozotocin-induced diabetic rats. In the present study, alpha, beta I, beta II, gamma, delta, and epsilon isoform-specific antibodies were used in parallel to the measurement of compound PKC activity for the characterization of PKC distribution and isoform expression in sciatic nerves of normal and diabetic rats. To distinguish isoform expression between the axonal and glial compartments, PKC isoforms were evaluated in nerves subjected to Wallerian degeneration and in a pure primary Schwann cell culture. alpha, beta I, beta II, delta, and epsilon but no gamma isoforms were detected in sciatic nerve. Similar immunoreactivity was observed in degenerated nerves 3-4 days after transection except for diminished beta I and epsilon species; in Schwann cell cultures, only alpha, beta II, delta, and epsilon were detected. In normal nerves, two-thirds of PKC compound activity was found in the cytosol and 50% of total enzyme activity translocated to the Na+,K(+)-ATPase-enriched membrane fraction with phorbol myristate acetate. Similar redistribution patterns were observed for the immunoreactivity of all isoforms with the exception of delta, which did not translocate to the membrane with phorbol myristate acetate. No abnormality in compound PKC activity, in the immunoreactive intensity, or in the distribution of PKC isoforms could be detected in rat sciatic nerve after 6-12 weeks of diabetes. Thus, defective activation rather than decreased intrinsic PKC activity may occur in diabetic neuropathy.

Animals↗
PubMed1994

Casein kinase II preferentially phosphorylates human tau isoforms containing an amino-terminal insert. Identification of threonine 39 as the primary phosphate acceptor.

The in vitro phosphorylation of the microtubule-associated protein tau by casein kinase II was studied. Purified human brain tau was phosphorylated by casein kinase II to a stoichiometry of 0.7 mol of 32P/mol of tau. Individual recombinant human tau isoforms were phosphorylated to stoichiometries ranging from 0.2 to 0.8 mol of 32P/mol of tau. Casein kinase II catalyzed a 4-fold greater incorporation of phosphate into the tau isoform containing a 58-amino acid insert near its amino terminus (T4L) than the isoforms without the 58-amino acid insert (T3 and T4). Phosphopeptide mapping of casein kinase II phosphorylated human tau and recombinant tau isoforms suggested that the isoforms containing an amino-terminal insert constitute the major substrates for casein kinase II within the tau family. The sites of phosphorylation on T4L were identified by digesting phosphorylated T4L with the protease Asp-N, separating the peptides by reversed phase high performance liquid chromatography, and analyzing the isolated peptides by liquid-secondary ion mass spectrometry and solid-phase amino-terminal sequencing. Thr39 was identified as the predominant phosphorylation site, which is located 5 residues from the amino-terminal insert in T4L. Phosphopeptide mapping of tau isolated from LA-N-5 neuroblastoma cells indicates that Thr39 is phosphorylated in situ. To our knowledge, this is the first demonstration of a differential phosphorylation of the human tau isoforms, with the isoforms containing the acidic amino-terminal insert being the preferred substrates of casein kinase II.

Amino Acid Sequence↗
PubMed1993

A new isoform of the laminin receptor integrin alpha 7 beta 1 is developmentally regulated in skeletal muscle.

Within the integrin family, there are two groups of receptors that bind laminin. One of these groups comprises the heterodimers alpha 3 beta 1, alpha 6 beta 1, and alpha 7 beta 1, all of which bind the E8 fragment of laminin, and whose alpha subunits show significant homology at the amino acid sequence level. alpha 3 and alpha 6 exist as isoforms with distinct cytoplasmic domains (termed A and B), suggesting that they may couple laminin adhesion to distinct cellular responses. We report the identification of a new alpha 7 mRNA which encodes an alpha 7 protein isoform with an alternative cytoplasmic domain. Based on homology with alpha 3 and alpha 6 isoforms, this new isoform is classified as alpha 7A and the previously published one as alpha 7B. This result extends the similarity between alpha 3, alpha 6, and alpha 7 laminin receptor subunits and suggests a common ancestral gene. The alpha 7 beta 1 laminin receptor was proposed to be involved in myogenic differentiation. However, alpha 7 isoforms were not investigated in that context. We detected the alpha 7B isoform mRNA in all tissues and cell types tested, including myocardial and skeletal muscle. In contrast, the alpha 7A isoform was detectable exclusively in skeletal muscle, not in myocardial muscle or cells or any other tissues or cell lines tested. Furthermore, the differentiating skeletal muscle cell line C2C12 expressed only alpha 7B at the replicating myoblast stage and acquired alpha 7A expression upon induction of differentiation and fusion. Splicing of alpha 7B mRNA in C2C12 occurred shortly after myogenin expression and could be an indicator of progression through the program of skeletal muscle differentiation.

Amino Acid Sequence↗
PubMed1993

Cell-CAM105 isoforms with different adhesion functions are coexpressed in adult rat tissues and during liver development.

The rat hepatocyte cell adhesion molecule cell-CAM105 has recently been shown to be composed of at least two isoforms. Expression of the two isoforms in different tissues and during fetal liver development in rats was studied by RNase protection using a probe which could specifically and simultaneously detect both isoforms. This probe revealed protected fragments of expected lengths for the L-form and the S-form in RNA samples isolated from various adult rat tissues. High levels of the L-form and S-form messages were detected in liver and intestine, moderate levels were detected in lung, and weak signals were detected in muscle, kidney, and spleen. In liver development studies, the messages for cell-CAM105 showed a major increase on the first day after birth compared to the fetal stage, and both isoform messages were proportionally increased. These results indicate that both cell-CAM105 isoforms may have function(s) related to hepatocyte differentiation. To study the adhesion function of cell-CAM105 isoforms, full-length cDNAs for these isoforms were expressed in insect cells. The insect cells expressing the L-form cell-CAM105 were found to aggregate. However, expression of S-form cell-CAM105 did not support cell aggregation. These results indicate that L-form, but not S-form, cell-CAM105 directly mediates the cell adhesion function.

Adenosine Triphosphatases↗
PubMed1995

The intranuclear amount of phospholipase C beta 1 decreases following cell differentiation in Friend cells, whereas gamma 1 isoform is not affected.

The existence of a signal transduction system in the nucleus, based on polyphosphoinositide breakdown mediated by specific phosphoinositidases (PLC), has been widely documented. In different cell systems, nuclear PLCs can be modulated, in response to agonists, either by enhancing or by down-regulating their activity, thus leading to DNA replication or to cell differentiation. Friend cells, induced to erythroid differentiation by dimethyl sulfoxide (DMSO), show a down-regulation of PLC beta 1 isoform, as indicated by the reduction of the transcription of its mRNA and of the in vitro synthesis of its translation product. The intracellular localization and the amount of different PLC isoforms have been evaluated by electron microscope immunocytochemistry. In untreated Friend cells, PLC beta 1 and gamma 1 isoforms are both present within the nucleus, whereas mainly the gamma 1 isoform is detected in the cytoplasm. The small amount of cytoplasmic PLC beta 1 is probably representative only of the newly synthesized enzyme. Quantitative immunolabeling analyses demonstrate that erythroid differentiation is associated with a significant decrease of the PLC beta 1 amount in the nucleus and with an almost complete disappearance of that isoform in the cytoplasm, whereas the PLC gamma 1 isoform is unaffected. The two PLC isoforms, moreover, appear to be differently associated with the nuclear components, PLC beta 1 being steadily bound to the inner nuclear matrix, whereas PLC gamma 1 is almost completely soluble.

Animals↗
PubMed1996

Expression of fibronectin ED-A+ and ED-B+ isoforms by human and experimental colorectal cancer. Contribution of cancer cells and tumor-associated myofibroblasts.

Alternative splicing of primary fibronectin (FN) mRNA results in the synthesis of different isoforms. ED-A+ and ED-B+ FN isoforms are absent from plasma FN and are representative of cellular FN. Their expression was studied in human and rat normal colon, in human colorectal carcinomas, and in transplanted tumors derived from a chemically-induced rat colon cancer. In normal colon, only the ED-A+ FN isoform was expressed as a thin deposit between crypt colonocytes and pericryptal myofibroblasts. Conversely, heavy ED-A+ FN deposits and lighter ED-B+ FN expression were found in the stroma of colorectal tumors in association with myofibroblasts surrounding tumor glands. Some colonic cancer cells also contained intracellular FN isoform granules and expressed FN mRNA. Tumor-associated myofibroblasts and some cancer cell lines were able to synthesize and deposit extracellular ED-A+ and ED-B+ FN in vitro. FN isoform deposition by tumor-associated myofibroblasts was not modulated by colon cancer cell-conditioned medium, but was strongly enhanced when myofibroblasts were cultured on colon cancer cell extracellular matrix or on laminin. These results show that the ED-A+ and ED-B+ FN isoforms were overexpressed in colorectal cancer. Cancer cells can deposit these FN isoforms directly and also stimulate their deposition by tumor-associated myofibroblasts.

Actins↗
PubMed1996

Myosin heavy chain isoforms regulate muscle function but not myofibril assembly.

Myosin heavy chain (MHC) is the motor protein of muscle thick filaments. Most organisms produce many muscle MHC isoforms with temporally and spatially regulated expression patterns. This suggests that isoforms of MHC have different characteristics necessary for defining specific muscle properties. The single Drosophila muscle Mhc gene yields various isoforms as a result of alternative RNA splicing. To determine whether this multiplicity of MHC isoforms is critical to myofibril assembly and function, we introduced a gene encoding only an embryonic MHC into Drosophila melanogaster. The embryonic transgene acts in a dominant antimorphic manner to disrupt flight muscle function. The transgene was genetically crossed into an MHC null background. Unexpectedly, transformed flies expressing only the embryonic isoform are viable. Adult muscles containing embryonic MHC assemble normally, indicating that the isoform of MHC does not determine the dramatic ultrastructural variation among different muscle types. However, transformed flies are flightless and show reduced jumping and mating ability. Their indirect flight muscle myofibrils progressively deteriorate. Our data show that the proper MHC isoform is critical for specialized muscle function and myofibril stability.

Animals↗
PubMedDate not supplied

Expression of CD44 standard and isoforms in human breast cancer xenografts and shedding of soluble forms into serum of nude mice.

Standard CD44 (CD44s) and variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas. In this work we addressed the question of whether these molecules are also expressed on xenografted human breast carcinomas and if certain expression patterns are correlated with biological parameters like tumour size, hormone receptor status, histology, growth rate, chemoresistance and microenvironment. Additionally, we were interested in the shedding of soluble CD44 (sCD44) into the blood circulation of tumour bearing nude mice. The human breast carcinomas MCF-7, MCF-7/ADR, 4296 and MDA-MB435, 4134 and 4151 were transplanted subcutaneously (sc.) or into the mammary fat pad (mfp.) of nude mice. The expression of the CD44s, -v6, and -v9 isoforms was determined at different time points on tissue samples by immunohistochemistry or RT-PCR employing human-specific antibodies or primers, respectively. The serum concentration of CD44s and -v6 was measured by human specific ELISAs. All tumours expressed CD44s. The lowest level was observed in the MCF-7 cancer. The CD44v6 and -v9 sequences and epitopes were distinctly expressed in MCF-7/ADR. MDA-MB435, 4134, 4151 and 4296, while MCF-7 lacked these isoforms. The highest serum concentration of the v6 isoform was detected in mice bearing the tumour 4296 with a high tendency for lymphogenic metastasis. The serum levels of sCD44 were in 5/6 xenografts linearly correlated with the tumour size. Interestingly, there was a remarkable difference between the two sublines MCF-7 and MCF-7/ADR: Both the tissue and serum levels of CD44 isoforms indicated that the development of multidrug resistance is accompanied by an alteration in the expression of membrane proteins discussed to be involved in metastasis. There was no relation of tissue expression with the transplantation site and the hormone receptor status of the tumour lines. CD44s and its variant isoforms are expressed in human xenotransplanted breast cancers in very different levels and patterns. The highest expression in the tumour 4296 is related to lymphogenic metastasis while the absence of isoforms in the model MCF-7 is related to non-metastatic behaviour. CD44 is shed into the serum and can be used for monitoring of tumour growth.

Alternative Splicing↗
PubMed1997

Transferrin isoform distribution: gender and alcohol consumption.

Transferrin (Tf) has different isoforms based on the degree of sialylation of its two N-linked oligosaccharide chains. The least sialylated isoforms of Tf; with 0 (asialo Tf), 1 (monosialo Tf), and 2 (disialo Tf) sialic acids are referred to as carbohydrate-deficient transferrin (CDT). CDT has been reported to be a specific and sensitive marker for the detection and monitoring of alcohol abuse. However, the possible differences between the three CDT isoforms in males and females relative to alcohol consumption has not been known. The present study included 82 males (M) and 43 females (F) with well documented drinking habits. The Tf isoforms were separated by FPLC and measured by RIA in the collected fractions, as well as by a commercially available method (CDTect RIA). The results were expressed as relative values and absolute values. Female low consumers compared to male low consumers had higher levels of asialo Tf (p < 0.01) and monosialo Tf (p < 0.01), but not of disialo Tf or sum of asialo, monosialo, and disialo Tf. Male high consumers and chronic consumers compared to male low consumers had 53% and 219% higher levels of asialo Tf, 4% and 28% higher monosialo Tf, 57% and 148% higher disialo Tf, and 48% and 134% higher sum of CDT isoforms, respectively. The corresponding increases in females were for asialo Tf 68% and 249%, for monosialo Tf 36% and 58%, for disialo Tf 54% and 225%, and for sum of CDT isoforms 52% and 192%, respectively. For both genders, total Tf, trisialo Tf, and the levels of more sialylated transferrin isoforms were constant when comparing the consumption groups. Results expressed as relative values and absolute values were in good agreement. In conclusion, the present study indicates that alcohol consumption strongly increases the levels of asialo Tf and disialo Tf and slightly increases the level of monosialo Tf. However, women had higher asialo Tf and monosialo Tf levels than men. Alcohol consumption does not increase trisialo or more sialyated Tf subfractions. Expressing the CDT results as absolute or relative values made no obvious difference in diagnostic efficiency.

Adult↗
PubMed1998

Influence of lipoprotein (a) levels and isoforms on fibrinolytic activity--study in families with high lipoprotein (a) levels.

Increased levels of lipoprotein (a) [Lp(a)] have been considered an independent risk factor for cardiovascular disease, but the mechanism behind this relationship is not completely understood. A high concentration of Lp(a) may interfere with fibrinolysis because of the structural similarity between apo(a) and plasminogen. The aim of the present study was to examine the influence of apo(a) levels and isoforms on fibrinolytic activity in 82 subjects from 24 families in which the Lp(a) levels were > or =30 mg/dl in at least one child and one parent. Several fibrinolytic parameters, including plasmin generation by fibrin-bound tissue plasminogen activator, the lipid profile and apo(a) isoforms were studied. Subjects with high circulating Lp(a) levels (n = 44) had significantly reduced plasmin generation compared with their relatives with normal Lp(a) levels (n = 38). A significant inverse correlation between Lp(a) levels and plasmin generation was observed. The individuals with a combination of high levels of plasma Lp(a) and a major apo(a) isoform < or =580 kD molecular weight show the lowest fibrinolytic activity. A high correlation was found between the levels of apo(a) isoforms in children and the levels of the corresponding parental apo(a) isoforms. We conclude that the antifibrinolytic effect of Lp(a) in subjects with two apo(a) isoforms may depend not only on the total plasma level of Lp(a) but also on the relative concentration of the small apo(a) isoform.

Adolescent↗