Hintergrund: Hepatische Sternzellen (HSC) sind perisinusoidal angesiedelte Mesenchymzellen und nehmen als aktivierte HSC eine zentrale Funktion bei der hepatischen Fibrogenese ein. Aufgrund der Tatsache, dass TIMP–1 die Matrix-Degradation unterbindet und aktivierte HSC vor Apoptose schützt, ist die Antagonisierung von TIMP–1 ein interessanter Ansatz für die Therapie der hepatischen Fibrose. Unser Ziel war die Antagonisierung von TIMP–1 (durch proteolytisch inaktive MMP–9 Mutanten), um den Schutz aktivierter HSC vor Apoptose zu durchbrechen.

Mitochondria play a crucial role in germination and early seedling growth in Arabidopsis (Arabidopsis thaliana). Morphological observations of mitochondria revealed that mitochondrial numbers, typical size, and oval morphology were evident after 12 h of imbibition in continuous light (following 48 h of stratification). The transition from a dormant to an active metabolic state was punctuated by an early molecular switch, characterized by a transient burst in the expression of genes encoding mitochondrial proteins. Factors involved in mitochondrial transcription and RNA processing were overrepresented among these early-expressed genes. This was closely followed by an increase in the transcript abundance of genes encoding proteins involved in mitochondrial DNA replication and translation. This burst in the expression of factors implicated in mitochondrial RNA and DNA metabolism was accompanied by an increase in transcripts encoding components required for nucleotide biosynthesis in the cytosol and increases in transcript abundance of specific members of the mitochondrial carrier protein family that have previously been associated with nucleotide transport into mitochondria. Only after these genes peaked in expression and largely declined were typical mitochondrial numbers and morphology observed. Subsequently, there was an increase in transcript abundance for various bioenergetic and metabolic functions of mitochondria. The coordination of nucleus- and organelle-encoded gene expression was also examined by quantitative reverse transcription-polymerase chain reaction, specifically for components of the mitochondrial electron transport chain and the chloroplastic photosynthetic machinery. Analysis of protein abundance using western-blot analysis and mass spectrometry revealed that for many proteins, patterns of protein and transcript abundance changes displayed significant positive correlations. A model for mitochondrial biogenesis during germination is proposed, in which an early increase in the abundance of transcripts encoding biogenesis functions (RNA metabolism and import components) precedes a later cascade of gene expression encoding the bioenergetic and metabolic functions of mitochondria.

Summary Mitochondria complex II (succinate dehydrogenase, SDH ) plays a central role in respiratory metabolism as a component of both the electron transport chain and the tricarboxylic acid cycle. We report the identification of an SDH assembly factor by analysis of T ‐ DNA insertions in A t5g51040, a protein with unknown function that was identified by mass spectrometry analysis as a low abundance mitochondrial protein. This gene is co‐expressed with a number of genes encoding mitochondrial proteins, including SDH 1‐1, and has low partial sequence similarity to human SDHAF 2, a protein required for flavin‐adenine dinucleotide (FAD) insertion into SDH . In contrast to observations of other SDH deficient lines in Arabidopsis, the sdhaf2 line did not affect photosynthetic rate or stomatal conductance, but instead showed inhibition of primary root elongation with early lateral root emergence, presumably due to the low SDH activity caused by the reduced abundance of SDHAF 2. Both roots and leaves showed succinate accumulation but different responses in the abundance of other organic acids and amino acids assayed. Isolated mitochondria showed lowered SDH 1 protein abundance, lowered maximal SDH activity and less protein‐bound flavin‐adenine dinucleotide (FAD) at the molecular mass of SDH 1 in the gel separation. The short root phenotype and SDH function of sdhaf2 was fully complemented by transformation with SDHAF 2 . Application of the SDH inhibitor, malonate, phenocopied the sdhaf2 root architecture in WT . Whole root respiratory assays showed no difference between WT and sdhaf2 , but micro‐respirometry of the tips of roots clearly showed low oxygen consumption in sdhaf2 which could explain a metabolic deficit responsible for root tip growth.

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Yield components of five regrowth cycles, two in 1981 and three in 1982, of three red clover (Trifolium pratense L.) populations and three alfalfa (Medicago sativa L.) cultivars were compared in swards. Red clover left more stubble but produced less herbage and accumulated total yield (herbage, stubble and 10 cm depth root) at a slower rate than alfalfa during most regrowths. The percent leaf at flowering of red clover was similar to that of alfalfa. Maximum LAI declined during successive regrowths each year. Maximum crop growth rates were 30 and 34 g m −2 d −1 for red clover and alfalfa, respectively. Stem development (canopy height) followed patterns of accumulation of herbage yield. The initiation of stems was slower in red clover and stem populations were less than that of alfalfa. Selection for faster stem initiation rates, higher stem populations, and reduced partitioning of dry matter towards stem bases which would be left as stubble were suggested as ways of increasing the herbage yield of red clover.Key words: Trifolium pratense L., Medicago sativa L., yield components, growth analysis clover (red), alfalfa

Background: The liver is sensitively prone to alterations in metal content and homeostasis. Most of its metabolic and catabolic functions depend on trace elements. Metals are either integral part of enzymes, cofactors, or directly serve as chemical catalysts. Therefore, a lack of trace elements can lead to organ failure or systemic illness. Conversely, excessive hepatic trace element deposition resulting from genetic disorders, intoxication, extensive dietary supply, or long-term parenteral nutrition cause hepatic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma.

Background: The LDL receptor-related protein–2 (Megalin) is the largest membrane receptor found in mammals and mediates the endocytic uptake of vitamin/protein binding complexes. Megalin is known to be expressed in the proximal tubules of the kidney and to play an important role during the embryonic development of the brain. The aim of this study was to investigate the expression of Megalin in liver and to assess its pathobiological function in vivo and in vitro. Methods: During CCl4-induced liver fibrosis in mice and after bile duct ligation in rats, hepatic Megalin expression was studied by RT-PCR and immunohistochemistry. Megalin expression in isolated rat hepatic stellate cells (HSC) was determined using RT-PCR, immunocytochemistry, and confocal laser scanning microscopy (CLSM). To analyze a potential role of Megalin in retinol transport, HSC were incubated with FITC-labeled retinol binding protein and the recombinant Megalin chaperone RAP (receptor associated protein), and fluorescein incorporation was determined by fluorescence-activated cell analysis. Results: In both rodent models of liver fibrosis, Megalin immunoreactivity correlates with the stage of fibrosis. Isolated HSC express Megalin, and CLSM indicates that Megalin co-localizes with retinol-storing multivesicular bodies of HSC. Upon treatment of HSC with RAP, Megalin expression increases markedly (2.8–7.6 x). Flow cytometry demonstrates that this induction is associated with an augmented incorporation of FITC-labeled retinol-binding protein. Conclusions: Megalin is a novel marker for activated HSC, and retinol uptake of HSC depends on the association of retinol-binding protein with Megalin. Megalin might regulate the retinol metabolism of HSC and could represent a molecular target for antifibrotic drug design.

Research Articles| February 01 1999 Assignment of CSRP1 encoding the LIM domain protein CRP1, to human chromosome 1q32 by fluorescence in situ hybridization Subject Area: Genetics M. Erdel; M. Erdel aInstitute of Medical Biology and Human Genetics and Search for other works by this author on: This Site PubMed Google Scholar R. Weiskirchen R. Weiskirchen bInstitute of Biochemistry, University of Innsbruck, Innsbruck (Austria) Search for other works by this author on: This Site PubMed Google Scholar Cytogenetics and Cell Genetics (1998) 83 (1-2): 10–11. https://doi.org/10.1159/000015152 Article history Published Online: February 01 1999 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation M. Erdel, R. Weiskirchen; Assignment of CSRP1 encoding the LIM domain protein CRP1, to human chromosome 1q32 by fluorescence in situ hybridization. Cytogenetics and Cell Genetics 1 July 1998; 83 (1-2): 10–11. https://doi.org/10.1159/000015152 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsCytogenetic and Genome Research Search Advanced Search Article PDF first page preview Close Modal This content is only available via PDF. 1999Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.

In addition to carbon tetrachloride (CCl4), thioacetamide (TAA) represents a second widely used model for the induction of experimental liver fibrosis, but can also be employed for the development of acute liver failure and liver tumours. While TAA itself is not hepatotoxic, its reactive metabolites covalently bind to proteins and lipids thereby causing oxidative stress and centrilobular necrosis. Compared with CCl4, TAA leads to more periportal infiltrates and more pronounced ductal proliferation. While TAA has been shown to induce liver fibrosis development in several different mouse strains, wide variations in the administration routes, doses and treatment durations have been reported. Therefore, an adoption of a universal standard operating procedure for the administration of TAA is urgently needed. For that purpose, we are presenting here two TAA models (intraperitoneal administration of 150 mg/kg of TAA three times per week for 11 weeks in rats, and TAA administration in drinking water at 300 mg/L for 2-4 months in mice) with which we have had success in reliably and reproducibly developing chronic liver injury and fibrosis.

The ability to isolate intact, functional mitochondria from plant tissues is a key technique in the study of the genome, proteome, and metabolic function of the plant mitochondrion. Traditionally, mitochondrial plant researchers have turned to specific plant systems and organs (such as potato tubers and pea shoots) from which mitochondria are readily isolated in large quantities. However, increasingly, research is focused on a small number of model species, and there is a need to adapt existing protocols to allow the isolation of mitochondria from these model species. Arguably, the most important of these is Arabidopsis thaliana, for which a formidable array of genetic resources is available. However, because of its relatively small size and the absence of large heterotrophic organs, Arabidopsis is a challenging plant from which to isolate mitochondria. Here, we present two methods for isolating mitochondria from Arabidopsis, either from heterotrophic cell suspension cultures or from hydroponic seedling cultures. We also present details of commonly used assays to assess the physical and functional integrity of the isolated organelles.