Cachectin: A Macrophage Protein that Induces a Catabolic State in Infected Animals

1987 ◽  
pp. 94-94
Author(s):  
A. Cerami
Keyword(s):  
Catabolic State ◽  
Macrophage Protein

scholarly journals Biochemical approaches for nutritional support of skeletal muscle protein metabolism during sepsis

2004 ◽  
Vol 17 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Thomas C. Vary ◽  
Christopher J. Lynch
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Metabolic Response ◽  
Muscle Protein ◽  
The Body ◽  
Integrated Analysis ◽  
Skeletal Muscle Protein ◽  
Catabolic State ◽  
N Metabolism ◽  
Induced Defects

Sepsis initiates a unique series of modifications in the homeostasis of N metabolism and profoundly alters the integration of inter-organ cooperatively in the overall N and energy economy of the host. The net effect of these alterations is an overall N catabolic state, which seriously compromises recovery and is semi-refractory to treatment with current therapies. These alterations lead to a functional redistribution of N (amino acids and proteins) and substrate metabolism among injured tissues and major body organs. The redistribution of amino acids and proteins results in a quantitative reordering of the usual pathways of C and N flow within and among regions of the body with a resultant depletion of the required substrates and cofactors in important organs. The metabolic response to sepsis is a highly integrated, complex series of reactions. To understand the regulation of the response to sepsis, a comprehensive, integrated analysis of the fundamental physiological relationships of key metabolic pathways and mechanisms in sepsis is essential. The catabolism of skeletal muscles, which is manifested by an increase in protein degradation and a decrease in synthesis, persists despite state-of-the-art nutritional care. Much effort has focused on the modulation of the overall amount of nutrients given to septic patients in a hope to improve efficiencies in utilisation and N economies, rather than the support of specific end-organ targets. The present review examines current understanding of the processes affected by sepsis and testable means to circumvent the sepsis-induced defects in protein synthesis in skeletal muscle through increasing provision of amino acids (leucine, glutamine, or arginine) that in turn act as nutrient signals to regulate a number of cellular processes.

Comparative Analysis of Metabolism of Medium-and Plasma Perfused Primary Pig Hepatocytes Cultured around a 3-D Membrane Network

2000 ◽  
Vol 23 (2) ◽  
pp. 104-110 ◽  
Author(s):  
J.K. Unger ◽  
G. Catapano ◽  
N.A. Horn ◽  
A. Schroers ◽  
J.C. Gerlach ◽  
...  
Keyword(s):  
Clinical Application ◽  
Cell Function ◽  
Cell Attachment ◽  
Culture Media ◽  
Enzyme Release ◽  
Liver Support ◽  
Bioreactor Cultures ◽  
Catabolic State ◽  
Cell Nutrition

Culture media are frequently used in the evaluation of metabolical functions of hepatocytes in hybrid liver support systems (hLSS). However, media compositions differ substantially from those of plasma. Therefore, our study was designed to investigate whether current in vitro studies with medium are suitable to assess the metabolical competence of hLSS-cultures during clinical application as well as to explore whether the cell nutrition with medium provides a suitable modus operandi for stand by cultivation. Paired bioreactor cultures were perfused with either Williams’ Medium E (MPB) or human plasma (PPB). About 6x108 primary pig hepatocytes (>97% viability) were cultured in three laboratory scale bioreactors designed according to Gerlach's bioreactor-concept. Different perfusion protocols were initiated after a standardised period allowing for cell attachment and reorganisation in aggregates. Whereas patterns of enzyme release were similar in both protocols the metabolical behaviour was different between MPB (anabolic state) and PPB (catabolic state). Furthermore, compared to MPB the lidocaine-MEGX-tests for PPB demonstrated lower MEGX-concentrations and a different reaction pattern. We conclude that the nutrition of hepatocytes with medium during the stand by period itself might influence the cell function and subsequently the efficacy of the hLSS-treatment during clinical application. (Int J Artif Organs 2000; 23: 104–10)

scholarly journals Mycobacterium tuberculosis Alters the Metalloprotease Activity of the COP9 Signalosome

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Lia Danelishvili ◽  
Lmar Babrak ◽  
Sasha J. Rose ◽  
Jamie Everman ◽  
Luiz E. Bermudez
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cop9 Signalosome ◽  
Virulence Determinants ◽  
Bacterial Survival ◽  
Phagocytic Cells ◽  
Content Type ◽  
Metalloprotease Activity ◽  
Macrophage Protein

ABSTRACT Inhibition of apoptotic death of macrophages by Mycobacterium tuberculosis represents an important mechanism of virulence that results in pathogen survival both in vitro and in vivo. To identify M. tuberculosis virulence determinants involved in the modulation of apoptosis, we previously screened a transposon bank of mutants in human macrophages, and an M. tuberculosis clone with a nonfunctional Rv3354 gene was identified as incompetent to suppress apoptosis. Here, we show that the Rv3354 gene encodes a protein kinase that is secreted within mononuclear phagocytic cells and is required for M. tuberculosis virulence. The Rv3354 effector targets the metalloprotease (JAMM) domain within subunit 5 of the COP9 signalosome (CSN5), resulting in suppression of apoptosis and in the destabilization of CSN function and regulatory cullin-RING ubiquitin E3 enzymatic activity. Our observation suggests that alteration of the metalloprotease activity of CSN by Rv3354 possibly prevents the ubiquitin-dependent proteolysis of M. tuberculosis-secreted proteins. IMPORTANCE Macrophage protein degradation is regulated by a protein complex called a signalosome. One of the signalosomes associated with activation of ubiquitin and protein labeling for degradation was found to interact with a secreted protein from M. tuberculosis, which binds to the complex and inactivates it. The interference with the ability to inactivate bacterial proteins secreted in the phagocyte cytosol may have crucial importance for bacterial survival within the phagocyte.

scholarly journals Regulation of endocrine and paracrine sources of Igfs and Gh receptor during compensatory growth in hybrid striped bass (Morone chrysops×Morone saxatilis)

2008 ◽  
Vol 199 (1) ◽  
pp. 81-94 ◽  
Author(s):  
Matthew E Picha ◽  
Marc J Turano ◽  
Christian K Tipsmark ◽  
Russell J Borski
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Striped Bass ◽  
Compensatory Growth ◽  
Morone Saxatilis ◽  
Type I ◽  
Hybrid Striped Bass ◽  
Morone Chrysops ◽  
Gh Receptor ◽  
Catabolic State

Compensatory growth (CG) is a period of growth acceleration that exceeds normal rates after animals are alleviated of certain growth-stunting conditions. In hybrid striped bass (HSB, Morone chrysops×Morone saxatilis), 3 weeks of complete feed restriction results in a catabolic state that, when relieved, renders a subsequent phase of CG. The catabolic state was characterized by depressed levels of hepatic Type I and II GH receptor (ghr1, ghr2) and igf1 mRNA, along with considerable decreases in plasma Igf1. The state of catabolism also resulted in significant declines in hepatic igf2 mRNA and in circulating 40 kDa Igf-binding protein (Igfbp). Skeletal muscle expression of ghr2 mRNA was significantly increased. Upon realimentation, specific growth rates (SGRs) were significantly higher than sized-matched controls, indicating a period of CG. Hepatic ghr1, ghr2, igf1 and igf2 mRNA levels along with plasma Igf1 and 40 kDa Igfbp increased rapidly during realimentation. Plasma Igf1 and total hepatic igf2 mRNA were significantly correlated to SGR throughout the study. Skeletal muscle igf1 mRNA also increased tenfold during CG. These data suggest that endocrine and paracrine/autocrine components of the GH–Igf axis, namely igf1, igf2, and ghr1 and ghr2, may be involved in CG responses in HSB, with several of the gene expression variables exceeding normal levels during CG. We also demonstrate that normalization of hepatic mRNA as a function of total liver production, rather than as a fraction of total RNA, may be a more biologically appropriate method of quantifying hepatic gene expression when using real-time PCR.

Sign in / Sign up

Export Citation Format

Share Document