scholarly journals The Recruitment-Secretory Block (“R-SB”) Phenomenon and Endoplasmic Reticulum Storage Diseases

2021 ◽  
Vol 22 (13) ◽  
pp. 6807
Author(s):  
Francesco Callea ◽  
Paolo Tomà ◽  
Emanuele Bellacchio
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Damage ◽  
Basic Knowledge ◽  
In Vivo Studies ◽  
Future Research ◽  
Secretory Proteins ◽  
Electron Microscopic ◽  
Apo B ◽  
Heterozygous Condition

In this article, we review the biological and clinical implication of the Recruitment-Secretory Block (“R-SB”) phenomenon. The phenomenon refers to the reaction of the liver with regard to protein secretion in conditions of clinical stimulation. Our basic knowledge of the process is due to the experimental work in animal models. Under basal conditions, the protein synthesis is mainly carried out by periportal (zone 1) hepatocytes that are considered the “professional” synthesizing protein cells. Under stimulation, midlobular and centrolobular (zone 2 and 3) hepatocytes, are progressively recruited according to lobular gradients and contribute to the increase of synthesis and secretion. The block of secretion, operated by exogenous agents, causes intracellular retention of all secretory proteins. The Pi MZ phenotype of Alpha-1-antitrypsin deficiency (AATD) has turned out to be the key for in vivo studies of the reaction of the liver, as synthesis and block of secretion are concomitant. Indeed, the M fraction of AAT is stimulated for synthesis and regularly exported while the Z fraction is mostly retained within the cell. For that reason, the phenomenon has been designated “Recruitment-Secretory Block” (“R-SB”). The “R-SB” phenomenon explains why: (a) the MZ individuals can correct the serum deficiency; (b) the resulting immonohistochemical and electron microscopic (EM) patterns are very peculiar and specific for the diagnosis of the Z mutation in tissue sections in the absence of genotyping; (c) the term carrier is no longer applicable for the heterozygous condition as all Pi MZ individuals undergo storage and the storage predisposes to liver damage. The storage represents the true elementary lesion and consequently reflects the phenotype-genotype correlation; (d) the site and function of the extrahepatic AAT and the relationship between intra and extracellular AAT; (e) last but not least, the concept of Endoplasmic Reticulum Storage Disease (ERSD) and of a new disease, hereditary hypofibrinogenemia with hepatic storage (HHHS). In the light of the emerging phenomenon, described in vitro, namely that M and Z AAT can form heteropolymers within hepatocytes as well as in circulation, we have reviewed the whole clinical and experimental material collected during forty years, in order to evaluate to what extent the polymerization phenomenon occurs in vivo. The paper summarizes similarities and differences between AAT and Fibrinogen as well as between the related diseases, AATD and HHHS. Indeed, fibrinogen gamma chain mutations undergo an aggregation process within the RER of hepatocytes similar to AATD. In addition, this work has clarified the intriguing phenomenon underlying a new syndrome, hereditary hypofibrinogenemia and hypo-APO-B-lipoproteinemia with hepatic storage of fibrinogen and APO-B lipoproteins. It is hoped that these studies could contribute to future research and select strategies aimed to simultaneously correct the hepatocytic storage, thus preventing the liver damage and the plasma deficiency of the two proteins.

scholarly journals Contribution to the biological interest of Valeriana officinalis: an update

2021 ◽  
Vol 42 ◽  
pp. e67649
Author(s):  
Marta Sánchez ◽  
Elena González-Burgos ◽  
Irene Iglesias ◽  
M. Pilar Gómez-Serranillos Cuadrado
Keyword(s):  
Clinical Trials ◽  
Nervous System ◽  
Biological Activities ◽  
In Vivo Studies ◽  
Neuroprotective Activity ◽  
Future Research ◽  
Valeriana Officinalis ◽  
Valerenic Acid

Valeriana officinalis L. (Caprifoliaceae family) has been traditionally used to treat mild nervous tension and sleep problems. The basis of these activities are mainly attributed to valerenic acid through the modulation of the GABA receptor. Moreover, V. officinalis is claimed to have other biological activities such as cardiovascular benefits, anticancer, antimicrobial and spasmolytic.  The current review aims to update the biological and pharmacological studies (in vitro, in vivo and clinical trials) of V. officinalis and its major secondary metabolites in order to guide future research. Databases PubMed, Science Direct and Scopus were used for literature search including original papers written in English and published between 2014 and 2020. There have been identified 33 articles which met inclusion criteria. Most of these works were performed with V. officinalis extracts and only a few papers (in vitro and in vivo studies) evaluated the activity of isolated compounds (valerenic acid and volvalerenal acid K). In vitro studies focused on studying antioxidant and neuroprotective activity. In vivo studies and clinical trials mainly investigated activities on the nervous system (anticonvulsant activity, antidepressant, cognitive problems, anxiety and sleep disorders). Just few studies were focused on other different activities, highlight effects on symptoms of premenstrual and postmenopausal syndromes. Valeriana officinalis continues to be one of the medicinal plants most used by today's society for its therapeutic properties and whose biological and pharmacological activities continue to arouse great scientific interest as evidenced in recent publications. This review shows scientific evidence on traditional uses of V. officinalis on nervous system.

scholarly journals AN ANALYSIS OF COLLAGEN SECRETION BY ESTABLISHED MOUSE FIBROBLAST LINES

1964 ◽  
Vol 22 (1) ◽  
pp. 227-258 ◽  
Author(s):  
Burton Goldberg ◽  
Howard Green
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Mouse Fibroblast ◽  
In Vivo Studies ◽  
In Vitro Synthesis ◽  
Collagen Secretion ◽  
Golgi System ◽  
Alternative Theories

In vitro synthesis of collagen by established mouse fibroblast lines has been examined by electron microscopy. During rapid growth (log phase), when collagen could not be detected in the cultures, the cells lacked a well developed granular ergastoplasm and Golgi system. Upon cessation of growth (stationary phase), collagen accumulated in the cultures and the cells demonstrated highly developed granular and smooth ergastoplasm. Collagen appeared to be synthesized in the rough-surfaced endoplasmic reticulum and to be transported as a soluble protein to the cell surface by vesicular elements of the agranular ergastoplasm. Fusion of the limiting membranes of these vesicles with the cell membrane permitted the discharge of the soluble collagen into the extracellular space, where fibrils of two diameter distributions formed. The secretion of collagen is concluded to be of the merocrine type. Alternative theories of collagen secretion are discussed and the data for established lines compared with the results of other in vitro and in vivo studies of collagen fibrillogenesis.

scholarly journals Hyperoxia, reactive oxygen species, and hyperventilation: oxygen sensitivity of brain stem neurons

2004 ◽  
Vol 96 (2) ◽  
pp. 784-791 ◽  
Author(s):  
Jay B. Dean ◽  
Daniel K. Mulkey ◽  
Richard A. Henderson ◽  
Stephanie J. Potter ◽  
Robert W. Putnam
Keyword(s):  
Oxidative Stress ◽  
Brain Stem ◽  
Brain Slices ◽  
Respiratory Control ◽  
In Vivo Studies ◽  
Future Research ◽  
Direct Effects ◽  
Underlying Assumption

Hyperoxia is a popular model of oxidative stress. However, hyperoxic gas mixtures are routinely used for chemical denervation of peripheral O2 receptors in in vivo studies of respiratory control. The underlying assumption whenever using hyperoxia is that there are no direct effects of molecular O2 and reactive O2 species (ROS) on brain stem function. In addition, control superfusates used routinely for in vitro studies of neurons in brain slices are, in fact, hyperoxic. Again, the assumption is that there are no direct effects of O2 and ROS on neuronal activity. Research contradicts this assumption by demonstrating that O2 has central effects on the brain stem respiratory centers and several effects on neurons in respiratory control areas; these need to be considered whenever hyperoxia is used. This mini-review summarizes the long-recognized, but seldom acknowledged, paradox of respiratory control known as hyperoxic hyperventilation. Several proposed mechanisms are discussed, including the recent hypothesis that hyperoxic hyperventilation is initiated by increased production of ROS during hyperoxia, which directly stimulates central CO2 chemoreceptors in the solitary complex. Hyperoxic hyperventilation may provide clues into the fundamental role of redox signaling and ROS in central control of breathing; moreover, oxidative stress may play a role in respiratory control dysfunction. The practical implications of brain stem O2 and ROS sensitivity are also considered relative to the present uses of hyperoxia in respiratory control research in humans, animals, and brain stem tissues. Recommendations for future research are also proposed.

scholarly journals The Emerging Role and Promise of Circular RNAs in Obesity and Related Metabolic Disorders

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1473
Author(s):  
Mohamed Zaiou
Keyword(s):  
Rna Binding ◽  
Metabolic Diseases ◽  
Rna Binding Proteins ◽  
In Vivo Studies ◽  
Future Research ◽  
Circular Rnas ◽  
Exciting Field ◽  
Rna Molecules

Circular RNAs (circRNAs) are genome transcripts that are produced from back-splicing of specific regions of pre-mRNA. These single-stranded RNA molecules are widely expressed across diverse phyla and many of them are stable and evolutionary conserved between species. Growing evidence suggests that many circRNAs function as master regulators of gene expression by influencing both transcription and translation processes. Mechanistically, circRNAs are predicted to act as endogenous microRNA (miRNA) sponges, interact with functional RNA-binding proteins (RBPs), and associate with elements of the transcriptional machinery in the nucleus. Evidence is mounting that dysregulation of circRNAs is closely related to the occurrence of a range of diseases including cancer and metabolic diseases. Indeed, there are several reports implicating circRNAs in cardiovascular diseases (CVD), diabetes, hypertension, and atherosclerosis. However, there is very little research addressing the potential role of these RNA transcripts in the occurrence and development of obesity. Emerging data from in vitro and in vivo studies suggest that circRNAs are novel players in adipogenesis, white adipose browning, obesity, obesity-induced inflammation, and insulin resistance. This study explores the current state of knowledge on circRNAs regulating molecular processes associated with adipogenesis and obesity, highlights some of the challenges encountered while studying circRNAs and suggests some perspectives for future research directions in this exciting field of study.

scholarly journals Assessing Visual Exploratory Activity of Athletes in Virtual Reality Using Head Motion Characteristics

Sensors ◽  
2021 ◽  
Vol 21 (11) ◽  
pp. 3728
Author(s):  
Markus Wirth ◽  
Sebastian Kohl ◽  
Stefan Gradl ◽  
Rosanna Farlock ◽  
Daniel Roth ◽  
...  
Keyword(s):  
Virtual Reality ◽  
Expert Knowledge ◽  
Body Movement ◽  
Assessment Method ◽  
Exploratory Activity ◽  
In Vivo Studies ◽  
Future Research ◽  
Performance Factors ◽  
In Vivo Experiments

Maximizing performance success in sports is about continuous learning and adaptation processes. Aside from physiological, technical and emotional performance factors, previous research focused on perceptual skills, revealing their importance for decision-making. This includes deriving relevant environmental information as a result of eye, head and body movement interaction. However, to evaluate visual exploratory activity (VEA), generally utilized laboratory settings have restrictions that disregard the representativeness of assessment environments and/or decouple coherent cognitive and motor tasks. In vivo studies, however, are costly and hard to reproduce. Furthermore, the application of elaborate methods like eye tracking are cumbersome to implement and necessitate expert knowledge to interpret results correctly. In this paper, we introduce a virtual reality-based reproducible assessment method allowing the evaluation of VEA. To give insights into perceptual-cognitive processes, an easily interpretable head movement-based metric, quantifying VEA of athletes, is investigated. Our results align with comparable in vivo experiments and consequently extend them by showing the validity of the implemented approach as well as the use of virtual reality to determine characteristics among different skill levels. The findings imply that the developed method could provide accurate assessments while improving the control, validity and interpretability, which in turn informs future research and developments.

Food Derived Bioactive Peptides for Health Enhancement and Management of Some Chronic Diseases

2019 ◽  
pp. 1-11
Author(s):  
A. F. Ogori ◽  
A. T. Girgih ◽  
J. O. Abu ◽  
M. O. Eke
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Molecular Mechanisms ◽  
Bioactive Peptides ◽  
Food Sources ◽  
In Vivo Studies ◽  
Future Research ◽  
Target Cells

The bioactive peptides produced by enzymatic hydrolysis, acid hydrolysis and fermentation approach have been identified and used widely in research. These methods are important in enhancement or prevention and management of chronic diseases that are ravaging the world such as type -2-diabetes, hypertension, oxidative stress, cancer, and obesity. Sources of bioactive peptides have been established ranging from plant to animal and marine foods that have pharmacological effects; however these effects are dependent on target cells and peptides structure and conformations.  Plants such as hemp and animal source such as milk among others validate the findings of In vitro and In-vivo studies and the efficiency of these bioactive peptides in the management of certain chronic diseases. This article reviews the literature on bioactive peptides with concern on food sources, production and bioactive peptides application in enhancement of health and management of hypertension, diabetes and oxidative stress.  Future research efforts on bioactive peptides should be directed towards elucidating specific sequenced bioactive peptides and their molecular mechanisms, through In-vivo and In-vitro studies for specific health condition in human using nutrigenomics and peptideomic approaches.

scholarly journals Food Derived Bioactive Peptides for Health Enhancement and Management of Some Chronic Diseases

2019 ◽  
pp. 1-11
Author(s):  
A. F. Ogori ◽  
A. T. Girgih ◽  
J. O. Abu ◽  
M. O. Eke
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Molecular Mechanisms ◽  
Bioactive Peptides ◽  
Food Sources ◽  
In Vivo Studies ◽  
Future Research ◽  
Target Cells

The bioactive peptides produced by enzymatic hydrolysis, acid hydrolysis and fermentation approach have been identified and used widely in research. These methods are important in enhancement or prevention and management of chronic diseases that are ravaging the world such as type -2-diabetes, hypertension, oxidative stress, cancer, and obesity. Sources of bioactive peptides have been established ranging from plant to animal and marine foods that have pharmacological effects; however these effects are dependent on target cells and peptides structure and conformations.  Plants such as hemp and animal source such as milk among others validate the findings of In vitro and In-vivo studies and the efficiency of these bioactive peptides in the management of certain chronic diseases. This article reviews the literature on bioactive peptides with concern on food sources, production and bioactive peptides application in enhancement of health and management of hypertension, diabetes and oxidative stress.  Future research efforts on bioactive peptides should be directed towards elucidating specific sequenced bioactive peptides and their molecular mechanisms, through In-vivo and In-vitro studies for specific health condition in human using nutrigenomics and peptideomic approaches.

Nutraceuticals with anti-inflammatory and anti-oxidant properties as intervention for reducing the health effects of fine particulate matter: Potential and Prospects

2021 ◽  
Vol 24 ◽  
Author(s):  
Tanwi Trushna ◽  
Amit K. Tripathi ◽  
Sindhuprava Rana ◽  
Rajnarayan R. Tiwari
Keyword(s):  
Air Pollution ◽  
Particulate Matter ◽  
Human Health ◽  
Health Effects ◽  
In Vivo Studies ◽  
Future Research ◽  
Individual Level ◽  
Anti Inflammatory

: Air pollution, especially particulate matter pollution adversely affects human health. A growing pool of evidence has emerged which underscores the potential of individual-level nutritional interventions in attenuating the adverse health impact of exposure to PM2.5. Although controlling emission and reducing the overall levels of air pollution remains the ultimate objective globally, the sustainable achievement of such a target and thus consequent protection of human health will require a substantial amount of time and concerted efforts worldwide. In the meantime, smaller-scale individual-level interventions that can counter the inflammatory or oxidative stress effects triggered by exposure to particulate matter may be utilized to ameliorate the health effects of PM2.5 pollution. One such intervention is incorporation of nutraceuticals in the diet. Here, we present a review of the evidence generated from various in vitro, in vivo and human studies regarding the effects of different anti-inflammatory and antioxidant nutraceuticals in ameliorating the health effects of particulate matter air pollution. The studies discussed in this review suggest that these nutraceuticals when consumed as a part of the diet, or as additional supplementation, can potentially negate the cellular level adverse effects of exposure to particulate pollution. The potential benefits of adopting a non-pharmacological diet-based approach to air pollution-induced disease management have also been discussed. We argue that before a nutraceuticals-based approach can be used for widespread public adoption, further research, especially human clinical trials, is essential to confirm the beneficial action of relevant nutraceuticals and to explore the safe limits of human supplementation and the risk of side effects. Future research should focus on systematically translating bench-based knowledge regarding nutraceuticals gained from in-vitro and in-vivo studies into clinically usable nutritional guidelines.

scholarly journals IN VIVO INCORPORATION OF 3H-GALACTOSE BY THYROID FOLLICULAR CELLS OF THE RAT, AS SHOWN BY ELECTRON MICROSCOPIC RADIOAUTOGRAPHY

1972 ◽  
Vol 20 (3) ◽  
pp. 220-224 ◽  
Author(s):  
A. HADDAD
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Apparatus ◽  
Rough Endoplasmic Reticulum ◽  
Side Chains ◽  
Follicular Cells ◽  
Electron Microscopic ◽  
Thyroid Follicular Cells ◽  
Apical Vesicles ◽  
Electron Microscopic Radioautography

Radioactive galactose was injected intravenously into rats and localized in thyroid follicular cells by electron microscopic radioautography at intervals ranging from 2.5 to 30 min after injection. The galactose label was mostly present in the Golgi apparatus at 2.5 min, with some of it in the adjacent rough endoplasmic reticulum. By 30 min, the label was found in apical vesicles and colloid. It was concluded that galactose is added to the carbohydrate side chains of incomplete thyroglobulin molecules during their travel through the cisternae of the endoplasmic reticulum into the Golgi apparatus; the uptake begins as this organelle is approached, but predominates within it. The thyroglobulin molecule which has thus been labeled is transported by the apical vesicles to the colloid.

scholarly journals Sac1p mediates the adenosine triphosphate transport into yeast endoplasmic reticulum that is required for protein translocation.

1995 ◽  
Vol 131 (6) ◽  
pp. 1377-1386 ◽  
Author(s):  
P Mayinger ◽  
V A Bankaitis ◽  
D I Meyer
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Translocation ◽  
Protein A ◽  
Lipid Vesicles ◽  
Secretory Proteins ◽  
Transport Activity ◽  
Vitro Assay ◽  
Microsomal Membranes

Protein translocation into the yeast endoplasmic reticulum requires the transport of ATP into the lumen of this organelle. Microsomal ATP transport activity was reconstituted into proteoliposomes to characterize and identify the transporter protein. A polypeptide was purified whose partial amino acid sequence demonstrated its identity to the product of the SAC1 gene. Accordingly, microsomal membranes isolated from strains harboring a deletion in the SAC1 gene (sac1 delta) were found to be deficient in ATP-transporting activity as well as severely compromised in their ability to translocate nascent prepro-alpha-factor and preprocarboxypeptidase Y. Proteins isolated from the microsomal membranes of a sac1 delta strain were incapable of stimulating ATP transport when reconstituted into the in vitro assay system. When immunopurified to homogeneity and incorporated into artificial lipid vesicles, Sac1p was shown to reconstitute ATP transport activity. Consistent with the requirement for ATP in the lumen of the ER to achieve the correct folding of secretory proteins, the sac1 delta strain was shown to have a severe defect in transport of procarboxypeptidase Y out of the ER and into the Golgi complex in vivo. The collective data indicate an intimate role for Sac1p in the transport of ATP into the ER lumen.

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