scholarly journals Changes in IGFs in cardiac tissue following myocardial infarction

1999 ◽  
Vol 163 (3) ◽  
pp. 433-445 ◽  
Author(s):  
KG Matthews ◽  
GP Devlin ◽  
JV Conaglen ◽  
SP Stuart ◽  
W Mervyn Aitken ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Binding Proteins ◽  
Cardiac Tissue ◽  
Apoptotic Cell ◽  
Specific Binding ◽  
Cell Types ◽  
Necrotic Tissue ◽  
Igf I ◽  
The Relationship

We have studied changes in the IGF axis in an ovine model of myocardial infarction (MI), in order to determine the relationship between time-based changes in post-infarct myocardium and IGF levels. IGF localization was studied by immunocytochemistry, production by in situ hybridization, and specific binding by radioligand studies. In surviving tissue, IGF-I peptide localized to cardiomyocytes, with strongest immunostaining at 1 and 2 days post-infarct in the immediate border area adjoining the infarct, where IGF-I mRNA also increased, reaching a maximum at 2 days. Binding of radiolabelled IGF-I in surviving tissue was initially lower than that seen in cardiomyocytes in control myocardium, subsequently increasing to become significantly greater by 6 days post-infarct. In necrotic tissue, IGF-I peptide was still detectable in cardiomyocytes at 0.5 days post-infarct, but had cleared from this area by 1 day, becoming detectable again at 6 days post-infarct in macrophages and fibroblasts infiltrating the repair zone. IGF-I mRNA was not detected in necrotic tissue until 6 days, when probe hybridized to macrophages and fibroblasts. Within the necrotic zone, high levels of radiolabelled IGF-I binding to a combination of receptors and binding proteins were observed in cardiomyocytes in islands of viable tissue located close to the border. Weak immunostaining for IGF-II was observed in cardiomyocytes of the surviving tissue. IGF-II mRNA was not detected in either surviving or necrotic areas. Binding of radiolabelled IGF-II was predominantly to macrophages in both surviving and infarct areas, although as with IGF-I, high levels of binding of radiolabelled IGF-II to a combination of receptors and binding proteins were observed in islands of viable tissue close to the border within the necrotic area. We conclude that, following MI, surviving cardiomyocytes at the infarct border show marked changes in IGF-I localization, production, and specific binding, indicating that the IGF axis is directly involved in post-infarct events, possibly in the maintenance of cardiac function by the induction of hypertrophy and in cell survival by decreasing apoptotic cell death, which has been demonstrated in other cell types.

THE IGF AXIS AT THE FETO-MATERNAL INTERFACE

2001 ◽  
Vol 9 (3) ◽  
pp. 173-196 ◽  
Author(s):  
M Westwood
Keyword(s):  
Binding Proteins ◽  
Specific Binding ◽  
Cell Types ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Igf Receptor ◽  
And Function ◽  
Insulin Like Growth Factors

The insulin-like growth factors IGF-I and -II have effects on metabolism, growth, proliferation and differentiation in many tissues and cell types and are therefore important modulators of multiple aspects of physiology. IGF actions are largely mediated via the type 1 IGF receptor, though both peptides, particularly IGF-II, can bind to a second receptor known as the type 2 IGF/mannose-6-phosphate receptor. Access to these receptors is controlled by a family of six highly specific binding proteins (IGFBPs 1–6). Originally, the IGFBPs were thought of as IGF inhibitors, since their affinity for ligand is substantially higher than that of the receptors. More recently however, it has become apparent that modification of the binding proteins, for example proteolyis, phosphorylation or association with extracellular matrix, can influence IGFBP affinity for IGF and therefore IGF bioavailability and function.

The induction of a specific protease for insulin-like growth factor binding protein-3 in the circulation during severe illness

1991 ◽  
Vol 130 (3) ◽  
pp. 469-NP ◽  
Author(s):  
S. C. Davies ◽  
J. A. H. Wass ◽  
R. J. M. Ross ◽  
A. M. Cotterill ◽  
C. R. Buchanan ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Specific Binding ◽  
Nitrogen Retention ◽  
Late Pregnancy ◽  
Severe Illness ◽  
Igf I ◽  
Catabolic State ◽  
Specific Protease ◽  
Circulating Levels ◽  
Igfbp 3

ABSTRACT The insulin-like growth factors (IGF-I and IGF-II) are almost completely bound in the circulation to specific binding proteins (IGFBPs). These IGFBPs appear to play a pivotal role in maintaining circulating levels and modulating the delivery of the IGFs to the tissues. A large proportion of the circulating IGFs are bound with high affinity to one of the binding proteins, IGFBP-3. The mechanism by which these IGFs are transferred from the circulatory pool to the tissue receptors is at present unclear. Recent studies in late pregnancy have demonstrated the presence of specific proteases which may modify the IGFBPs such that their affinities for the IGFs are reduced. In this paper, we have demonstrated the presence of a heat-sensitive cation-dependent proteolytic enzyme specific for IGFBP-3 in the serum of five severely ill patients. The activity of this protease was found to vary in these patients, becoming more apparent during fasting than when studied after commencement of parenteral nutrition, indicating that one of the influencing factors in the activity of this protease is the nutritional intake of the patient. Age- and sex-matched healthy adults were also studied in a similar protocol, but no proteolytic modification of any of the IGFBPs was found in any of the samples examined. As the levels of both IGF-I and IGF-II were found to be low in the patients, the presence of a circulatory protease suggests that this may be an adaptive response to increase the bioavailability of the IGFs and possibly to improve the nitrogen retention and counter the catabolic state in severe illness. Journal of Endocrinology (1991) 130,469–473

scholarly journals miR-375 mediates CRH signaling pathway in inhibiting E2 synthesis in porcine ovary

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Chulin Yu ◽  
Meiling Li ◽  
Yue Wang ◽  
Ying Liu ◽  
Chengzhi Yan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Reproductive System ◽  
Follicular Development ◽  
Cell Types ◽  
Signaling System ◽  
Key Factor ◽  
The Relationship

The corticotropin-releasing hormone (CRH) signaling system is involved in numbers of stress-related physiological and pathological responses, including its inhibiting effects on estradiol (E2) synthesis and follicular development in the ovary. In addition, there are reports that microRNAs (miRNAs) can control the function of animal reproductive system. The aim of present study was to investigate the functions of miR-375 and the relationship between miR-375 and CRH signaling molecules in the porcine ovary. First, our common PCR results show that miR-375 and the CRH receptor 1 (CRHR1) are expressed in porcine ovary, whereas CRH receptor 2 (CRHR2) is not detected. We further have located the cell types of miR-375 and CRHR1 by in situ hybridization (ISH), and the results show that miR-375 is located only in the granulosa cells, whereas CRHR1 is positive in all of granulosa cells and oocytes, inferring that miR-375 and CRHR1 are co-localized in granulosa cells. Second, we show that overexpression of miR-375 in cultured granulosa cells suppresses the E2 production, whereas miR-375 knockdown demonstrates the opposite result. Besides, our in vitro results demonstrate that miR-375 mediates the signaling pathway of CRH inhibiting E2 synthesis. Finally, our data show that the action of miR-375 is accomplished by directly binding to the 3′UTR of specificity protein1 (SP1) mRNA to decrease the SP1 protein level. Thus, we conclude that miR-375 is a key factor in regulating E2 synthesis by mediating the CRH signaling pathway.

Insulin-like growth factors and their binding proteins in pleural fluid

1997 ◽  
pp. 467-473 ◽  
Author(s):  
Y Le Bouc ◽  
A Bellocq ◽  
C Philippe ◽  
L Perin ◽  
M Garabedian ◽  
...  
Keyword(s):  
Growth Factors ◽  
Pleural Fluid ◽  
Binding Proteins ◽  
Specific Binding ◽  
Gel Filtration ◽  
Specific Protein ◽  
Hydroxyvitamin D ◽  
Igf I ◽  
Acid Gel ◽  
Insulin Like Growth Factors

We investigated the expression and potential regulatory role of insulin-like growth factors (IGFs) and their specific binding proteins (BPs) in tuberculous and nontuberculous pleuritis. By using a radioimmunoassay after acid gel filtration chromatography, we found that mean concentrations of IGF-I were 211.9 +/- 20.2 microg/l and 203.2 +/- 31.1 microg/l in pleural fluid of 14 patients with tuberculous pleuritis and 9 patients with malignant pleuritis respectively. These values were near those in serum of the same patients (221.3 +/- 19.5 microg/l and 204.6 +/- 21.0 microg/l respectively). By using a specific protein-binding assay, we found that mean concentrations of IGF-II were 345.3 +/- 61.0 microg/l and 167.6 +/- 22.7 microg/l in tuberculous and malignant pleural effusions respectively. These values were significantly lower than those in serum of the same patients (628.3 +/- 79.0 microg/l, P<0.025 and 532.0 +/- 85.9 microg/l, P<0.025 respectively). Because bioavailability and bioactivity of IGFs may be regulated by their binding to IGFBPs, we studied IGFBP patterns in the pleural fluid of 6 patients with tuberculous pleuritis. As assessed by Western ligand blotting the levels of IGFBP-1 and IGFBP-2 were increased whereas those of IGFBP-3 were decreased in pleural fluid in comparison with serum. The decrease in IGFPB-3 levels reflected increased proteolysis, as assessed by Western immunoblotting. In spite of this presence of IGFBPs, IGFs could be responsible for the local biosynthesis of 1.25-dihydroxyvitamin D (1,25-(OH)2D) since pleural fluid levels of both IGF-I and IGF-II significantly correlated with those of 1,25-(OH)2D. These results indicate that IGFs are detectable in pleural fluid and may contribute to control the activity of 25-hydroxyvitamin D-1alpha hydroxylase in tuberculous pleuritis.

scholarly journals The 14-3-3τ Phosphoserine-Binding Protein Is Required for Cardiomyocyte Survival

2006 ◽  
Vol 27 (4) ◽  
pp. 1455-1466 ◽  
Author(s):  
Jeffrey M. C. Lau ◽  
Xiaohua Jin ◽  
Jie Ren ◽  
Joan Avery ◽  
Brian J. DeBosch ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Tissue ◽  
Ventricular Remodeling ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Experimental Myocardial Infarction ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Activation ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT 14-3-3 family members are intracellular dimeric phosphoserine-binding proteins that regulate signal transduction, cell cycle, apoptotic, and metabolic cascades. Previous work with global 14-3-3 protein inhibitors suggested that these proteins play a critical role in antagonizing apoptotic cell death in response to provocative stimuli. To determine the specific role of one family member in apoptosis, mice were generated with targeted disruption of the 14-3-3τ gene. 14-3-3τ−/− mice did not survive embryonic development, but haploinsufficient mice appeared normal at birth and were fertile. Cultured adult cardiomyocytes derived from 14-3-3τ+/− mice were sensitized to apoptosis in response to hydrogen peroxide or UV irradiation. 14-3-3τ+/− mice were intolerant of experimental myocardial infarction and developed pathological ventricular remodeling with increased cardiomyocyte apoptosis. ASK1, c-jun NH2-terminal kinase, and p38 mitogen-activated protein kinase (MAPK) activation was increased, but extracellular signal-regulated kinase MAPK activation was reduced, in 14-3-3τ+/− cardiac tissue. Inhibition of p38 MAPK increased survival in 14-3-3τ+/− mice subjected to myocardial infarction. These results demonstrate that 14-3-3τ plays a critical antiapoptotic function in cardiomyocytes and that therapeutic agents that increase 14-3-3τ activity may be beneficial to patients with myocardial infarction.

Insulin-like growth factor-binding proteins in tissue fluids from the lamb

1991 ◽  
Vol 129 (1) ◽  
pp. 59-68 ◽  
Author(s):  
A. P. D. Lord ◽  
A. A. Martin ◽  
P. E. Walton ◽  
F. J. Ballard ◽  
L. C. Read
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Specific Binding ◽  
Binding Protein ◽  
Extracellular Fluid ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Igf I ◽  
Acid Labile Subunit

ABSTRACT Heparinized samples of plasma, cerebrospinal fluid (CSF) and lymph from intestinal, prescapular and popliteal lymph nodes were collected from young lambs in order to characterize and compare the insulin-like growth factor-binding proteins (IGFBPs) in extracellular fluids with those from the circulation. Prior to collection and analysis, the superiority of heparin for plasma preparation was established over EDTA and citrate or the use of serum, according to the extent of IGF-I and IGF-II binding achieved in the high molecular mass IGFBP region in vitro. The IGFBPs were characterized by ligand blotting and competitive binding techniques using radiolabelled IGF-I, IGF-II and the truncated IGF analogue, des(1–3)IGF-I, as well as by ligand blotting of fractions after Superose 6 chromatography of incubations of fluids with labelled factors. This combined analysis demonstrated an IGF-II-specific binding protein at approximately 250 kDa that was present in plasma and each lymph type and presumably represented the soluble type-2 IGF receptor; a complex of 130 kDa containing 52 kDa and 46 kDa binding proteins that was labelled by all three IGF peptides was particularly evident in plasma and intestinal lymph and was probably a complex between IGFBP-3 and the acid-labile subunit; and a group of binding proteins that chromatographed as IGF complexes at approximately 50 kDa. This last group contained IGFBP bands of 52, 46, 35, 28 and 23·5 kDa in plasma and all lymphs as well as an IGF-II-specific band of 22 kDa in prescapular and popliteal lymphs. CSF differed qualitatively from plasma and lymph in that the 52/46 kDa IGFBP bands were undetectable in this fluid; the 35 kDa band was the predominant binding protein, and neither this nor the 28, 23·5 and 22 kDa proteins bound des(1–3)IGF-I to any significant extent. The 52,46 and 28 kDa bands in plasma and lymph did bind this ligand. Immunoblots using antisera against bovine IGFBP-2 showed binding at 35 kDa in all fluids as well as several bands at lower molecular masses. Taken together these results show not only marked differences in the binding protein profiles of sheep plasma, lymph and CSF, but both qualitative and quantitative differences between intestinal, prescapular and popliteal lymphs. We speculate that the differences between lymphs may result from tissuespecific release of binding proteins into extracellular fluid. Journal of Endocrinology (1991) 129, 59–68

Nuclear envelopes: Structure and biochemistry of the nuclear envelope

1974 ◽  
Vol 268 (891) ◽  
pp. 67-93 ◽  
Keyword(s):  
Nuclear Genome ◽  
Cell Types ◽  
Structure Lipid ◽  
Attachment Sites ◽  
Enzyme Pattern ◽  
The Stability ◽  
Pore Complexes ◽  
The Relationship ◽  
Kinetics Of

The ultrastructure of the nuclear evelope is described in various cell types with special emphasis on its pore complexes (p.c.). The architecture of the p.c. is defined against the properties of other membranous pore formations. Evidence is presented that the non-membranous p.c. components contain ribonucleoproteins but do not represent the attachment sites of nuclear chromatin. The possible dynamic nature of the p.c. material is discussed in relation to nucleocytoplasmic translocation processes. DNA of the nuclear genome is firmly attached to interporous sections of the inner nuclear membrane. The stability of this attachment is demonstrated, and chemical and conformational characteristics as well as periods and kinetics of replication are given for both isolated membrane DNA and the corresponding chromatin in situ . The membrane-associated chromatin is dominated by a heterochromatinous character; it does not represent a transitory membrane interaction of replicating DNA. It is hypothesized that membraneattachment of specific regions of the chromosomes are a means to their ordered arrangement during interphase and prophase. Structure, lipid, protein and enzyme pattern of the nuclear membranes, as well as the incorporation kinetics, underline the relationship to the endoplasmic reticulum.

Omega speckles - a novel class of nuclear speckles containing hnRNPs associated with noncoding hsr-omega RNA in Drosophila

2000 ◽  
Vol 113 (19) ◽  
pp. 3485-3497 ◽  
Author(s):  
K.V. Prasanth ◽  
T.K. Rajendra ◽  
A.K. Lal ◽  
S.C. Lakhotia
Keyword(s):  
Heat Shock ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cell Types ◽  
Immunocytochemical Staining ◽  
Nuclear Speckles ◽  
Omega Speckles ◽  
The Individual

Fluorescence RNA:RNA in situ hybridization studies in various larval and adult cell types of Drosophila melanogaster showed that the noncoding hsr-omega nuclear (hsromega-n) transcripts were present in the form of many small speckles. These speckles, which we name ‘omega speckles’, were distributed in the interchromatin space in close proximity to the chromatin. The only chromosomal site where hsromega-n transcripts localized was the 93D locus or the hsromega gene itself. The number of nucleoplasmic speckles varied in different cell types. Heat shock, which inhibits general chromosomal transcription, caused the individual speckles to coalesce into larger but fewer clusters. In extreme cases, only a single large cluster of hsromega-n transcripts localizing to the hsromega locus was seen in each nucleus. In situ immunocytochemical staining using antibodies against heterogenous nuclear RNA binding proteins (hnRNPs) like HRB87F, Hrp40, Hrb57A and S5 revealed that, in all cell types, all the hnRNPs gave a diffuse staining of chromatin areas and in addition, were present as large numbers of speckles. Colocalization studies revealed an absolute colocalization of the hnRNPs and the omegaspeckles. Heat shock caused all the hnRNPs to cluster together exactly, following the hsromega-n transcripts. Immunoprecipitation studies using the hnRNP antibodies further demonstrated a physical association of hnRNPs and hsromega transcripts. The omegaspeckles are distinct from interchromatin granules since nuclear speckles containing serine/arginine-rich SR-proteins like SC35 and SRp55 did not colocalize with the ω speckles. The speckled distribution of hnRNPs was completely disrupted in hsromega nullosomics. We conclude that the hsromega-n transcripts play essential structural and functional roles in organizing and establishing the hnRNP-containing omega speckles and thus regulate the trafficking and availability of hnRNPs and other related RNA binding proteins in the cell nucleus.

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