scholarly journals Reciprocal Crosstalk Between Autophagic and Endocrine Signaling in Metabolic Homeostasis

2016 ◽  
Vol 38 (1) ◽  
pp. 69-102 ◽  
Author(s):  
Rohit A. Sinha ◽  
Brijesh K. Singh ◽  
Paul M. Yen

Abstract Autophagy is a cellular quality control and energy-providing process that is under strict control by intra- and extracellular stimuli. Recently, there has been an exponential increase in autophagy research and its implications for mammalian physiology. Autophagy deregulation is now being implicated in many human diseases, and its modulation has shown promising results in several preclinical studies. However, despite the initial discovery of autophagy as a hormone-regulated process by De Duve in the early 1960s, endocrine regulation of autophagy still remains poorly understood. In this review, we provide a critical summary of our present understanding of the basic mechanism of autophagy, its regulation by endocrine hormones, and its contribution to endocrine and metabolic homeostasis under physiological and pathological settings. Understanding the cross-regulation of hormones and autophagy on endocrine cell signaling and function will provide new insight into mammalian physiology as well as promote the development of new therapeutic strategies involving modulation of autophagy in endocrine and metabolic disorders.

2005 ◽  
Vol 27 (1) ◽  
pp. 17-46 ◽  
Author(s):  
Henry N. Jabbour ◽  
Rodney W. Kelly ◽  
Hamish M. Fraser ◽  
Hilary O. D. Critchley

In women, endometrial morphology and function undergo characteristic changes every menstrual cycle. These changes are crucial for perpetuation of the species and are orchestrated to prepare the endometrium for implantation of a conceptus. In the absence of pregnancy, the human endometrium is sloughed off at menstruation over a period of a few days. Tissue repair, growth, angiogenesis, differentiation, and receptivity ensue to prepare the endometrium for implantation in the next cycle. Ovarian sex steroids through interaction with different cognate nuclear receptors regulate the expression of a cascade of local factors within the endometrium that act in an autocrine/paracrine and even intracrine manner. Such interactions initiate complex events within the endometrium that are crucial for implantation and, in the absence thereof, normal menstruation. A clearer understanding of regulation of normal endometrial function will provide an insight into causes of menstrual dysfunction such as menorrhagia (heavy menstrual bleeding) and dysmenorrhea (painful periods). The molecular pathways that precipitate these pathologies remain largely undefined. Future research efforts to provide greater insight into these pathways will lead to the development of novel drugs that would target identified aberrations in expression and/or of local uterine factors that are crucial for normal endometrial function.


2015 ◽  
Vol 12 (102) ◽  
pp. 20141117 ◽  
Author(s):  
Marian Breuer ◽  
Kevin M. Rosso ◽  
Jochen Blumberger ◽  
Julea N. Butt

Multi-haem cytochromes are employed by a range of microorganisms to transport electrons over distances of up to tens of nanometres. Perhaps the most spectacular utilization of these proteins is in the reduction of extracellular solid substrates, including electrodes and insoluble mineral oxides of Fe(III) and Mn(III/IV), by species of Shewanella and Geobacter. However, multi-haem cytochromes are found in numerous and phylogenetically diverse prokaryotes where they participate in electron transfer and redox catalysis that contributes to biogeochemical cycling of N, S and Fe on the global scale. These properties of multi-haem cytochromes have attracted much interest and contributed to advances in bioenergy applications and bioremediation of contaminated soils. Looking forward, there are opportunities to engage multi-haem cytochromes for biological photovoltaic cells, microbial electrosynthesis and developing bespoke molecular devices. As a consequence, it is timely to review our present understanding of these proteins and we do this here with a focus on the multitude of functionally diverse multi-haem cytochromes in Shewanella oneidensis MR-1. We draw on findings from experimental and computational approaches which ideally complement each other in the study of these systems: computational methods can interpret experimentally determined properties in terms of molecular structure to cast light on the relation between structure and function. We show how this synergy has contributed to our understanding of multi-haem cytochromes and can be expected to continue to do so for greater insight into natural processes and their informed exploitation in biotechnologies.


Author(s):  
Peter Sterling

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.


2019 ◽  
Vol 14 (6) ◽  
pp. 470-479 ◽  
Author(s):  
Nazia Parveen ◽  
Amen Shamim ◽  
Seunghee Cho ◽  
Kyeong Kyu Kim

Background: Although most nucleotides in the genome form canonical double-stranded B-DNA, many repeated sequences transiently present as non-canonical conformations (non-B DNA) such as triplexes, quadruplexes, Z-DNA, cruciforms, and slipped/hairpins. Those noncanonical DNAs (ncDNAs) are not only associated with many genetic events such as replication, transcription, and recombination, but are also related to the genetic instability that results in the predisposition to disease. Due to the crucial roles of ncDNAs in cellular and genetic functions, various computational methods have been implemented to predict sequence motifs that generate ncDNA. Objective: Here, we review strategies for the identification of ncDNA motifs across the whole genome, which is necessary for further understanding and investigation of the structure and function of ncDNAs. Conclusion: There is a great demand for computational prediction of non-canonical DNAs that play key functional roles in gene expression and genome biology. In this study, we review the currently available computational methods for predicting the non-canonical DNAs in the genome. Current studies not only provide an insight into the computational methods for predicting the secondary structures of DNA but also increase our understanding of the roles of non-canonical DNA in the genome.


Author(s):  
Daniel Elieh Ali Komi ◽  
Wolfgang M. Kuebler

AbstractMast cells (MCs) are critically involved in microbial defense by releasing antimicrobial peptides (such as cathelicidin LL-37 and defensins) and phagocytosis of microbes. In past years, it has become evident that in addition MCs may eliminate invading pathogens by ejection of web-like structures of DNA strands embedded with proteins known together as extracellular traps (ETs). Upon stimulation of resting MCs with various microorganisms, their products (including superantigens and toxins), or synthetic chemicals, MCs become activated and enter into a multistage process that includes disintegration of the nuclear membrane, release of chromatin into the cytoplasm, adhesion of cytoplasmic granules on the emerging DNA web, and ejection of the complex into the extracellular space. This so-called ETosis is often associated with cell death of the producing MC, and the type of stimulus potentially determines the ratio of surviving vs. killed MCs. Comparison of different microorganisms with specific elimination characteristics such as S pyogenes (eliminated by MCs only through extracellular mechanisms), S aureus (removed by phagocytosis), fungi, and parasites has revealed important aspects of MC extracellular trap (MCET) biology. Molecular studies identified that the formation of MCET depends on NADPH oxidase-generated reactive oxygen species (ROS). In this review, we summarize the present state-of-the-art on the biological relevance of MCETosis, and its underlying molecular and cellular mechanisms. We also provide an overview over the techniques used to study the structure and function of MCETs, including electron microscopy and fluorescence microscopy using specific monoclonal antibodies (mAbs) to detect MCET-associated proteins such as tryptase and histones, and cell-impermeant DNA dyes for labeling of extracellular DNA. Comparing the type and biofunction of further MCET decorating proteins with ETs produced by other immune cells may help provide a better insight into MCET biology in the pathogenesis of autoimmune and inflammatory disorders as well as microbial defense.


2016 ◽  
Vol 310 (1) ◽  
pp. E1-E14 ◽  
Author(s):  
Caterina Constantinou ◽  
Eleni A. Karavia ◽  
Eva Xepapadaki ◽  
Peristera-Ioanna Petropoulou ◽  
Eugenia Papakosta ◽  
...  

Emerging evidence strongly supports that changes in the HDL metabolic pathway, which result in changes in HDL proteome and function, appear to have a causative impact on a number of metabolic disorders. Here, we provide a critical review of the most recent and novel findings correlating HDL properties and functionality with various pathophysiological processes and disease states, such as obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, inflammation and sepsis, bone and obstructive pulmonary diseases, and brain disorders.


Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2541-2553 ◽  
Author(s):  
Johanna Laurikkala ◽  
Johanna Pispa ◽  
Han-Sung Jung ◽  
Pekka Nieminen ◽  
Marja Mikkola ◽  
...  

X-linked and autosomal forms of anhidrotic ectodermal dysplasia syndromes (HED) are characterized by deficient development of several ectodermal organs, including hair, teeth and exocrine glands. The recent cloning of the genes that underlie these syndromes, ectodysplasin (ED1) and the ectodysplasin A receptor (EDAR), and their identification as a novel TNF ligand-receptor pair suggested a role for TNF signaling in embryonic morphogenesis. In the mouse, the genes of the spontaneous mutations Tabby (Ta) and downless (dl) were identified as homologs of ED1 and EDAR, respectively. To gain insight into the function of this signaling pathway in development of skin and hair follicles, we analyzed the expression and regulation of Eda and Edar in wild type as well as Tabby and Lef1 mutant mouse embryos. We show that Eda and Edar expression is confined to the ectoderm and occurs in a pattern that suggests a role of ectodysplasin/Edar signaling in the interactions between the ectodermal compartments and the formation and function of hair placodes. By using skin explant cultures, we further show that this signaling pathway is intimately associated with interactions between the epithelial and mesenchymal tissues. We also find that Ta mutants lack completely the placodes of the first developing tylotrich hairs, and that they do not show patterned expression of placodal genes, including Bmp4, Lef1, Shh, Ptch and Edar, and the genes for β-catenin and activin A. Finally, we identified activin as a mesenchymal signal that stimulates Edar expression and WNT as a signal that induces Eda expression, suggesting a hierarchy of distinct signaling pathways in the development of skin and hair follicles. In conclusion, we suggest that Eda and Edar are associated with the onset of ectodermal patterning and that ectodysplasin/edar signaling also regulates the morphogenesis of hair follicles.


2017 ◽  
Vol 19 (5) ◽  
pp. 3498-3505 ◽  
Author(s):  
Kenichi Koizumi ◽  
Katsuyuki Nobusada ◽  
Mauro Boero

Reaction mechanism of CO molecules onto a Cu/CeO2 surface and morphological changes.


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