scholarly journals LIVER SINUSOIDAL CELLS

1972 ◽  
Vol 54 (1) ◽  
pp. 107-119 ◽  
Author(s):  
D. Montgomery Bissell ◽  
Lydia Hammaker ◽  
Rudi Schmid
Keyword(s):  
Cell Population ◽  
Cellular Localization ◽  
Isolated Cells ◽  
Sulfur Colloid ◽  
Sinusoidal Cells ◽  
Heat Treated ◽  
Sinusoidal Cell ◽  
Liver Sinusoidal Cells

Sequestration and degradation of red blood cells (RBC) are believed to occur in part in the liver, but the magnitude and cellular localization of this process remain uncertain. This problem was studied in rats by investigating isolated parenchymal and sinusoidal cell populations of the liver. After digesting the perfused liver with pronase, hepatic sinusoidal cells were isolated free of RBC and debris. Of the isolated cells, 90% were phagocytic, as judged by their uptake of colloidal 198Au or of aggregated albumin-131I administered in vivo After administration of spherocytic (heat-treated) RBC, however, only about one quarter of the isolated cells were found to contain phagocytized RBC. This apparently distinct population of RBC-phagocytizing cells is designated as "erythrophagocytic (EP)" cells. The EP cell population was further characterized functionally by its specific phagocytosis of colloidal carbon and of 99mtechnetium-sulfur colloid and histochemically by its peroxidase activity. The role of the EP population in the catabolism of RBC-hemoglobin was studied in isolated hepatic sinusoidal cells by assay of microsomal heme oxygenase (MHO), which is the inducible enzyme system that converts heme to bilirubin. The MHO activity of individual sinusoidal isolates was related directly to their content of EP cells Assay of the MHO activity of the whole spleen and of the total EP cell population of the liver suggested that these two tissues may be of comparable importance in their ability to degrade RBC-hemoglobin.

Abstract 356: Krueppel-Like Factor 15 Regulates Wnt/β-Catenin Transcription and Controls Cardiac Progenitor Cell Fate in the Postnatal Heart

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Claudia Noack ◽  
Maria P Zafiriou ◽  
Anke Renger ◽  
Hans J Schaeffer ◽  
Martin W Bergmann ◽  
...  
Keyword(s):  
Cell Fate ◽  
Transcriptional Activation ◽  
Progenitor Cell ◽  
Cellular Localization ◽  
Target Genes ◽  
Critical Role ◽  
Isolated Cells ◽  
Cardiac Progenitor Cell

Wnt/β-catenin signaling controls adult heart remodeling partly by regulating cardiac progenitor cell (CPC) differentiation. We now identified and characterized a novel cardiac interaction of the transcription factor Krueppel-like factor 15 (KLF15) with the Wnt/β-catenin signaling on adult CPCs. In vitro mutation, reporter gene assays and co-localization studies revealed that KLF15 requires two distinct domains for nuclear localization and for repression of β-catenin-mediated transcription. KLF15 had no effect on β-catenin stability or cellular localization, but interacted with its co-factor TCF4, which is required for activation of β-catenin target gene expression. Moreover, increased TCF4 ubiquitination was induced by KLF15. In line with this finding we found KLF15 to interact with the Nemo-like kinase, which was shown to phosphorylate and target TCF4 for degradation. In vivo analyses of adult Klf15 functional knock-out (KO) vs. wild-type (WT) mice showed a cardiac β-catenin-mediated transcriptional activation and reduced TCF4 degradation along with cardiac dysfunction assessed by echocardiography (n=10). FACS analysis of the CPC enriched-population of KO vs. WT mice revealed a significant reduction of cardiogenic-committed precursors identified as Sca1+/αMHC+ (0.8±0.2% vs. 1.8±0.1%) and Tbx5+ (3.5±0.3% vs. 5.2±0.5%). In contrast, endothelial Sca1+/CD31+ cells were significantly higher in KO mice (11.3±0.4% vs. 8.6±0.4%; n≥9). In addition, Sca1+ isolated cells of Klf15 KO showed increased RNA expression of endothelial markers von Willebrand Factor, CD105, and Flk1 along with upregulation of β-catenin target genes. CPCs co-cultured on adult fibroblasts resulted in increased endothelial Flk1 cells and reduction of αMHC and Hand1 cardiogenic cells in KO vs. WT CPCs (n=9). Treating these co-cultures with Quercetin, an inhibitor of nuclear β-catenin, resulted in partial rescue of the observed phenotype. This study uncovers a critical role of KLF15 for the maintenance of cardiac tissue homeostasis. Via inhibition of β-catenin transcription, KLF15 controls cardiomyogenic cell fate similar to embryonic cardiogenesis. This knowledge may provide a tool for activation of endogenous CPCs in the postnatal heart.

scholarly journals PR55α regulatory subunit of PP2A inhibits the MOB1/LATS cascade and activates YAP in pancreatic cancer cells

Oncogenesis ◽  
2019 ◽  
Vol 8 (11) ◽  
Author(s):  
Ashley L. Hein ◽  
Nichole D. Brandquist ◽  
Caroline Y. Ouellette ◽  
Parthasarathy Seshacharyulu ◽  
Charles A. Enke ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cellular Localization ◽  
Activation Mechanism ◽  
Regulatory Subunit ◽  
Loss Of Function ◽  
Anchorage Independent Growth ◽  
Pancreatic Cancer Cells

Abstract PP2A holoenzyme complexes are responsible for the majority of Ser/Thr phosphatase activities in human cells. Each PP2A consists of a catalytic subunit (C), a scaffold subunit (A), and a regulatory subunit (B). While the A and C subunits each exists only in two highly conserved isoforms, a large number of B subunits share no homology, which determines PP2A substrate specificity and cellular localization. It is anticipated that different PP2A holoenzymes play distinct roles in cellular signaling networks, whereas PP2A has only generally been defined as a putative tumor suppressor, which is mostly based on the loss-of-function studies using pharmacological or biological inhibitors for the highly conserved A or C subunit of PP2A. Recent studies of specific pathways indicate that some PP2A complexes also possess tumor-promoting functions. We have previously reported an essential role of PR55α, a PP2A regulatory subunit, in the support of oncogenic phenotypes, including in vivo tumorigenicity/metastasis of pancreatic cancer cells. In this report, we have elucidated a novel role of PR55α-regulated PP2A in the activation of YAP oncoprotein, whose function is required for anchorage-independent growth during oncogenesis of solid tumors. Our data show two lines of YAP regulation by PR55α: (1) PR55α inhibits the MOB1-triggered autoactivation of LATS1/2 kinases, the core member of the Hippo pathway that inhibits YAP by inducing its proteasomal degradation and cytoplasmic retention and (2) PR55α directly interacts with and regulates YAP itself. Accordingly, PR55α is essential for YAP-promoted gene transcriptions, as well as for anchorage-independent growth, in which YAP plays a key role. In summary, current findings demonstrate a novel YAP activation mechanism based on the PR55α-regulated PP2A phosphatase.

scholarly journals The Role of Liver Sinusoidal Cells in Hepatocyte-Directed Gene Transfer

2010 ◽  
Vol 176 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Frank Jacobs ◽  
Eddie Wisse ◽  
Bart De Geest
Keyword(s):  
Gene Transfer ◽  
Sinusoidal Cells ◽  
Liver Sinusoidal Cells

scholarly journals Dynamic patterns of YAP1 expression and cellular localization in the developing and injured utricle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vikrant Borse ◽  
Matthew Barton ◽  
Harry Arndt ◽  
Tejbeer Kaur ◽  
Mark E. Warchol
Keyword(s):  
Inner Ear ◽  
Cellular Localization ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Hippo Signaling ◽  
Supporting Cells ◽  
The Hippo Pathway

AbstractThe Hippo signaling pathway is a key regulator of tissue development and regeneration. Activation of the Hippo pathway leads to nuclear translocation of the YAP1 transcriptional coactivator, resulting in changes in gene expression and cell cycle entry. Recent studies have demonstrated the nuclear translocation of YAP1 during the development of the sensory organs of the inner ear, but the possible role of YAP1 in sensory regeneration of the inner ear is unclear. The present study characterized the cellular localization of YAP1 in the utricles of mice and chicks, both under normal conditions and after HC injury. During neonatal development, YAP1 expression was observed in the cytoplasm of supporting cells, and was transiently expressed in the cytoplasm of some differentiating hair cells. We also observed temporary nuclear translocation of YAP1 in supporting cells of the mouse utricle after short periods in organotypic culture. However, little or no nuclear translocation of YAP1 was observed in the utricles of neonatal or mature mice after ototoxic injury. In contrast, substantial YAP1 nuclear translocation was observed in the chicken utricle after streptomycin treatment in vitro and in vivo. Together, these data suggest that differences in YAP1 signaling may partially account for the differing regenerative abilities of the avian vs. mammalian inner ear.

scholarly journals Studies in vivo of the tissue uptake, cellular distribution and catabolic turnover of exogenous glucocerebrosidase in rat

1981 ◽  
Vol 194 (3) ◽  
pp. 733-742 ◽  
Author(s):  
S Morrone ◽  
P G Pentchev ◽  
J Baynes ◽  
S Thorpe
Keyword(s):  
Process Analysis ◽  
Parenchymal Cell ◽  
Cell Uptake ◽  
Cellular Distribution ◽  
Liver Uptake ◽  
Sinusoidal Cells ◽  
Exogenous Enzyme ◽  
Sinusoidal Cell ◽  
Rate Of Decline

The kinetics of plasma clearance of highly purified human placental glucocerebrosidase in rats were biphasic with 75% of the infused dose showing a rapid clearance (t1/2 = 11 min) and the remaining 25% a considerably lower rate (t1/2 = 60 min). The majority of the enzyme (60%) was taken up by the liver. Although saturation kinetics for the clearance or uptake were not observed, the very high hepatic endocytic index (217 microliter/min) of glucocerebrosidase uptake indicated that liver uptake was mediated by an adsorptive endocytic process. Analysis of the cellular distribution of recovered glucocerebrosidase revealed predominantly parenchymal cell uptake with 38% of the exogenous enzyme in hepatocytes and only 2% in sinusoidal cells. High-mannose glycoproteins blocked hepatocyte and sinusoidal cell uptake of glucocerebrosidase equally. Kinetic experiments failed to demonstrate a transfer or shuttle of exogenous glucocerebrosidase from sinusoidal cells to hepatocytes. The possibility was raised that uptake of enzyme by the liver may be mediated by a common receptor that functions in both hepatocytes and sinusoidal cells. The catabolic turnover of exogenous glucocerebrosidase in rat liver was biphasic and the rate of decline was similar in hepatocytes and sinusoidal cells.

scholarly journals Adsorptive pinocytosis of 125I-labelled lactate dehydrogenase isoenzymes H4 and M4 by rat yolk sacs incubated in vitro

1981 ◽  
Vol 198 (3) ◽  
pp. 587-593 ◽  
Author(s):  
T Kooistra ◽  
K E Williams
Keyword(s):  
Lactate Dehydrogenase ◽  
Hydrophobic Interactions ◽  
Dissociation Constants ◽  
Yolk Sac ◽  
Sinusoidal Cells ◽  
Membrane Complex ◽  
Liver Sinusoidal Cells ◽  
Lactate Dehydrogenase Isoenzymes

The pinocytic uptake of 125I-labelled porcine lactate dehydrogenase isoenzymes H4 and M4 by 17.5-day rat visceral yolk sac incubated in vitro was saturable and binding obeyed Michaelis-Menten kinetics. The uptake characteristics of the two isoenzymes were very similar. For the H4 and the M4 isoenzymes, the dissociation constants of the protein-plasma-membrane complex were 0.62 microM and 0.84 microM respectively, and the maximum rates of uptake 0.13 and 0.26 nmol/mg of yolk-sac protein per h respectively. These findings contrast with those from studies in vivo, which show the M4 form is taken up by rat liver sinusoidal cells at a much higher rate than the H4 form, and point to different recognition systems for the adsorptive pinocytosis of simple non-conjugate proteins in yolk-sac epithelial cells and liver sinusoidal cells. Competition experiments indicate that binding of the H4 isoenzyme to the yolk-sac cells is restricted to hydrophobic interactions, whereas the binding of the M4 isoenzyme involves hydrophobic as well as positively charged sites on the protein molecules.

scholarly journals Role of the Modular Domains of SR Proteins in Subnuclear Localization and Alternative Splicing Specificity

1997 ◽  
Vol 138 (2) ◽  
pp. 225-238 ◽  
Author(s):  
Javier F. Cáceres ◽  
Tom Misteli ◽  
Gavin R. Screaton ◽  
David L. Spector ◽  
Adrian R. Krainer
Keyword(s):  
Alternative Splicing ◽  
Splice Site ◽  
Site Selection ◽  
Cellular Localization ◽  
Sr Proteins ◽  
Dependent Manner ◽  
Splice Site Selection ◽  
Subnuclear Localization

SR proteins are required for constitutive pre-mRNA splicing and also regulate alternative splice site selection in a concentration-dependent manner. They have a modular structure that consists of one or two RNA-recognition motifs (RRMs) and a COOH-terminal arginine/serine-rich domain (RS domain). We have analyzed the role of the individual domains of these closely related proteins in cellular distribution, subnuclear localization, and regulation of alternative splicing in vivo. We observed striking differences in the localization signals present in several human SR proteins. In contrast to earlier studies of RS domains in the Drosophila suppressor-of-white-apricot (SWAP) and Transformer (Tra) alternative splicing factors, we found that the RS domain of SF2/ASF is neither necessary nor sufficient for targeting to the nuclear speckles. Although this RS domain is a nuclear localization signal, subnuclear targeting to the speckles requires at least two of the three constituent domains of SF2/ASF, which contain additive and redundant signals. In contrast, in two SR proteins that have a single RRM (SC35 and SRp20), the RS domain is both necessary and sufficient as a targeting signal to the speckles. We also show that RRM2 of SF2/ASF plays an important role in alternative splicing specificity: deletion of this domain results in a protein that, although active in alternative splicing, has altered specificity in 5′ splice site selection. These results demonstrate the modularity of SR proteins and the importance of individual domains for their cellular localization and alternative splicing function in vivo.

scholarly journals Stress signaling by Tec tyrosine kinase in the ischemic myocardium

2010 ◽  
Vol 299 (3) ◽  
pp. H713-H722 ◽  
Author(s):  
Michael J. Zhang ◽  
Sarah Franklin ◽  
Yifeng Li ◽  
Sujing Wang ◽  
Xiaochen Ru ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Ischemia Reperfusion ◽  
Intracellular Localization ◽  
Cardiac Injury ◽  
Ischemic Injury ◽  
Isolated Cells ◽  
Cardiac Phenotype ◽  
Nonreceptor Tyrosine Kinases

Nonreceptor tyrosine kinases have an increasingly appreciated role in cardiac injury and protection. To investigate novel tasks for members of the Tec family of nonreceptor tyrosine kinases in cardiac phenotype, we examined the behavior of the Tec isoform in myocardial ischemic injury. Ischemia-reperfusion, but not cardiac protective agents, induced altered intracellular localization of Tec, highlighting distinct actions of this protein compared with other isoforms, such as Bmx, in the same model. Tec is abundantly expressed in cardiac myocytes and assumes a diffuse intracellular localization under basal conditions but is recruited to striated structures upon various stimuli, including ATP. To characterize Tec signaling targets in vivo, we performed an exhaustive proteomic analysis of Tec-binding partners. These experiments expand the role of the Tec family in the heart, identifying the Tec isoform as an ischemic injury-induced isoform, and map the subproteome of its interactors in isolated cells.

Carbonic anhydrase activity and aminopyrine uptake in isolated gastric mucosal cells

1984 ◽  
Vol 247 (3) ◽  
pp. G213-G219
Author(s):  
A. Wollin
Keyword(s):  
Carbonic Anhydrase ◽  
Acid Secretion ◽  
Carbonic Anhydrase Activity ◽  
Isolated Cells ◽  
Oxyntic Cell ◽  
Mucosal Cells ◽  
Cell Fractions ◽  
Isolated Cell

The role of carbonic anhydrase in the regulation and production of gastric acid was examined. Studies were done on isolated rabbit fundic mucosal cells, in which carbonic anhydrase activity and [14C]aminopyrine uptake were measured. The oxyntic cell-enriched cell fractions had the largest carbonic anhydrase content (4.2 +/- 0.1 U/10(6) cells) compared with other mucosal cells. The cellular carbonic anhydrase content of all isolated cell fractions was primarily a soluble enzyme, accounting for 10% of the total mucosal enzyme quantity. The remainder was found in the incubation medium from the mucosal dispersion procedure. The remaining cellular carbonic anhydrase activity in the oxyntic cell fraction was not enhanced by secretagogues. [14C]aminopyrine uptake increased dose dependently in the presence of histamine and dibutyryl cAMP. Acetazolamide (0.2 mM) inhibited the cellular carbonic anhydrase activity (99%) but did not interfere with the cellular uptake of [14C]aminopyrine. The present data from isolated cells suggest that cellular carbonic anhydrase in the oxyntic cell does not appear to be an integral step in the initiation of secretory function of isolated oxyntic cells. The lack of interference by the carbonic anhydrase inhibitor with H+ production does not exclude a role for carbonic anhydrase at high levels of acid secretion as it may occur in vivo, since isolated oxyntic cells probably do not achieve maximal rates of acid secretion and aminopyrine uptake reflects acid gradients and not rate of acid secretion.

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