[
Biochem Soc Trans,
2003]
Heparan sulphate (HS) acts as a multifunctional cell regulator, with specific sulphated saccharide sequences designed for selective interactions with many proteins. Functionally, these interactions result in regulation of the protein activities, and there is growing evidence that cells can dynamically alter the structure of HS sequences that they display. HS biosynthesis involves the action of a complex set of enzymes with polymerase, epimerase and sulphotransferase (ST) activities. in higher organisms, multiple isoforms of STs decorate the nascent HS chains with specific patterns of sulphation that confer selective biological functions. The study of HSSTs in model organisms provides a valuable opportunity to examine the expression of these enzymes in relation to the structure and activities of the HS produced. Here we describe that, in mice, there are stage-specific combinations of HSST isoenzymes that underlie the synthesis of different HS species at different times in the developing brain. This differential expression of HSSTs results in the synthesis of structurally variant HS species that form functional signalling complexes with specific fibroblast growth factors and their receptors. Regulated synthesis of specific HS species could be a mechanism for the regulation of proliferation and differentiation in the developing brain. We also describe evidence that a Coenorhabditis elegans orthologue of the mammalian 20ST enzyme, called HST-2, is essential for the normal development of this nematode. Together, these studies emphasize the importance of HSSTs in the biosynthesis of functionally variant HS proteoglycans, and demonstrate the importance of these complex regulatory molecules in developmental processes.
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Environ Sci Pollut Res Int,
2008]
GOAL, SCOPE AND BACKGROUND: Freshwater bodies which chemistry is dominated by dissolved humic substances (HS) seem to be the major type on Earth, due to huge non-calcareous geological formations in the Northern Hemisphere and in the tropics. Based on the paradigm of the inertness of being organic, direct interactions of dissolved HS with freshwater organisms are mostly neglected. However, dissolved organic carbon, the majority of which being HS, are natural environmental chemicals and should therefore directly interact with organisms. Major results that widened our perspective on humic substance ecology come from experiments with the compost nematode, Caenorhabditis elegans, which behaved contradictorily to textbook knowledge and provoked an in-depth re-consideration of some paradigms. APPROACH: To overcome old paradigms on HS and their potential interactions with organisms, we reviewed recent international literature, as well as ''grey'' literature. We also include results from own ongoing studies. RESULTS: This review focuses on direct interactions of dissolved HS with freshwater organisms and disregards indirect effects, such as under-water light quenching. Instead we show with some macrophyte and algal species that HS adversely interfere with photosynthesis and growth, whereby closely related algal species show different response patterns. In addition to this, HS suppress cyanobacteria more than eukaryotic algae. Quinones in the HS appear to be the effective structure. Furthermore, HS can modulate the offspring numbers in the nematode C. elegans and cause feminization of fish and amphibians--they possess hormone-like properties. The ecological consequences of this potential remain obscure at present. HS also have the potential to act as chemical attractants as shown with C. elegans and exert a mild chemical stress upon aquatic organisms in many ways: induction of molecular chaperons (stress proteins), induction and modulation of biotransformation and anti-oxidant enzymes. Furthermore, they produce an oxidative stress with lipidperoxidation as one clear symptom or even stress defense strategy. Stronger chemical stresses by HS may even lead to teratogenic effects as shown with fish embryos; all physiological responses to HS-mediated stress require energy, which were compensated on the expense of yolk as shown with zebra fish embryos. One Finnish field survey supports the view of a strong chemical stress, as the weight yield in fish species decreases with increasing HS content in the lakes. DISCUSSION: HS exert a variety of stress symptoms in aquatic and compost organisms. According to current paradigms of ecotoxicology, these symptoms have to be considered adverse, because their compensation consumes energy which is deducted from the main metabolism. However, the nematode C. elegans looks actively for such stressful environments, and this behavior is only understandable in the light of new paradigms of aging mechanisms, particularly the Green Theory of Aging. In this respect, we discuss the mild HS-mediated stress to aquatic and compost organisms. New empirical findings with HS themselves and HS building blocks appear to be consistent with this emerging paradigm and show that the individual lifespan may be expanded. At present the ecological consequences of these findings remain obscure. However, a multiple-stress resistance may be acquired which improves the individual fitness in a fluctuating environment. CONCLUSIONS: It appears that dissolved HS have to be considered abiotic ecological driving forces, somewhat less obvious than temperature, nutrients, or light. PERSPECTIVES: The understanding of the ecological control by dissolved humic substances is still fragmentary and needs to be studied in more details.
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Biochim Biophys Acta,
2017]
The mitochondrial role in carcinogenesis and cancer progression is an area of active research, with many unresolved questions. Various aspects of altered mitochondrial function have been implicated in tumorigenesis and tumor progression, including mitochondrial dysfunction, a metabolic switch to aerobic glycolysis, and dysregulation of mitophagy. Mitophagy is a highly specific quality control process which eliminates dysfunctional mitochondria and promotes mitochondrial turnover, and is involved in the adaptation to nutrient stress by controlling mitochondrial mass. The dysregulation of mitochondrial turnover has both a positive and negative role in cancer. This review will begin with a basic overview of the molecular mechanisms of mitophagy, and highlight recent trends in mitophagy from cancer studies. We will conclude this review by discussing areas of research in normal mitophagy that have yet to be explored in the context of cancer such as mitochondrial proteases, the mitochondrial unfolded protein response, and mitokine action. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.
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J Exp Biol,
2014]
The ability of each cell within a metazoan to adapt to and survive environmental and physiological stress requires cellular stress-response mechanisms, such as the heat shock response (HSR). Recent advances reveal that cellular proteostasis and stress responses in metazoans are regulated by multiple layers of intercellular communication. This ensures that an imbalance of proteostasis that occurs within any single tissue 'at risk' is protected by a compensatory activation of a stress response in adjacent tissues that confers a community protective response. While each cell expresses the machinery for heat shock (HS) gene expression, the HSR is regulated cell non-autonomously in multicellular organisms, by neuronal signaling to the somatic tissues, and by transcellular chaperone signaling between somatic tissues and from somatic tissues to neurons. These cell non-autonomous processes ensure that the organismal HSR is orchestrated across multiple tissues and that transmission of stress signals between tissues can also override the neuronal control to reset cell- and tissue-specific proteostasis. Here, we discuss emerging concepts and insights into the complex cell non-autonomous mechanisms that control stress responses in metazoans and highlight the importance of intercellular communication for proteostasis maintenance in multicellular organisms.