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Biomedicine & Pharmacotherapy =... Jun 2024The endoplasmic reticulum (ER) is important to cells because of its essential functions, including synthesizing three major nutrients and ion transport. When cellular... (Review)
Review
The endoplasmic reticulum (ER) is important to cells because of its essential functions, including synthesizing three major nutrients and ion transport. When cellular homeostasis is disrupted, ER quality control (ERQC) system is activated effectively to remove misfolded and unfolded proteins through ER-phagy, ER-related degradation (ERAD), and molecular chaperones. When unfolded protein response (UPR) and ER stress are activated, the cell may be suffering a huge blow, and the most probable consequence is apoptosis. The membrane contact points between the ER and sub-organelles contribute to communication between the organelles. The decrease in oxygen concentration affects the morphology and structure of the ER, thereby affecting its function and further disrupting the stable state of cells, leading to the occurrence of disease. In this study, we describe the functions of ER-, ERQC-, and ER-related membrane contact points and their changes under hypoxia, which will help us further understand ER and treat ER-related diseases.
Topics: Endoplasmic Reticulum; Humans; Animals; Endoplasmic Reticulum Stress; Unfolded Protein Response; Hypoxia; Apoptosis; Cell Hypoxia; Endoplasmic Reticulum-Associated Degradation
PubMed: 38781866
DOI: 10.1016/j.biopha.2024.116812 -
Experimental Cell Research Oct 2023Nonalcoholic fatty liver disease (NAFLD) is a type of steatosis not associated with excessive alcohol intake and includes nonalcoholic steatohepatitis (NASH), which can...
Nonalcoholic fatty liver disease (NAFLD) is a type of steatosis not associated with excessive alcohol intake and includes nonalcoholic steatohepatitis (NASH), which can progress to advanced fibrosis and hepatocellular carcinoma. Mitochondrial dysfunction causes oxidative stress, triggering hepatocyte death and inflammation; therefore, the present study aimed to explore relationship between mitochondrial carriers and oxidative stress. Firstly, we established a high fat diet (HFD)-fed ICR mouse NAFLD model characterized by obesity with insulin resistance and found transcriptional upregulation of Slc25a17 and downregulation of Slc25a3 (isoform B) and Slc25a13 in their fatty liver. A mitochondrial phosphate and Cu carrier, SLC25A3, was further studied in wild-type (wt) and SLC25A3-defective HepG2 cells (C1 and C3). SLC25A3 deficiency had insignificant effect on mitochondrial membrane potential (MtMP) and oxygen consumption rate (OCR) in untreated cells but suppressed them when cells were exposed to oleic acid. C1 and C3 cells were prone to produce reactive oxygen species (ROS), and increased ROS was associated with reduced mRNA expression of glutathione peroxidase (GPX) 1 and glutathione disulfide reductase (GSX) in these cell lines. Interestingly, cytoplasmic and mitochondrial Cu accumulation significantly reduced in C1 cells, demonstrating a predominant contribution of SLC25A3 to Cu transport into mitochondrial matrix. Cytotoxicity of free fatty acids was unchanged between wt and SLC25A3-deficient cells. These results indicate that reduced expression of SLC25A3 in fatty liver contributes to electron leak from mitochondria by limiting Cu availability, rendering hepatocytes more susceptible to oxidative stress. This study provides evidence that SLC25A3 is a novel risk factor for developing NASH.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Liver; Reactive Oxygen Species; Mice, Inbred ICR; Oxidative Stress; Mitochondria; Mitochondrial Membrane Transport Proteins
PubMed: 37557977
DOI: 10.1016/j.yexcr.2023.113740 -
Chemosphere Jan 2024Titanium dioxide (TiO)-based photocatalysts have gained increasing attention for their versatile applications in organic degradation, hydrogen production, air... (Review)
Review
Titanium dioxide (TiO)-based photocatalysts have gained increasing attention for their versatile applications in organic degradation, hydrogen production, air purification, and CO reduction. Various TiO-based heterojunction structures, including type I, type II, Schottky junction, Z-scheme, and S-scheme, have been extensively studied. The current research frontier is centered on the engineering modifications of TiO-based nanoheterojunction photocatalysts, such as defect engineering, morphological engineering, crystal phase/facet engineering, and multijunction engineering. These modifications enhance carrier transport, separation, and light absorption, thereby improving the photocatalytic performance. Remarkably, this aspect has been less addressed in existing reviews. This review aims to fill this gap by focusing on the engineering modifications of TiO-based nanoheterojunction photocatalysts. We delve into specific topics like oxygen vacancies, n-p homojunctions, and double defects. The review also systematically discusses the applications of multidimensional heterojunctions and examines carrier transport pathways in heterophase/facet junctions and their interactions with heterojunctions. A comprehensive summary of multijunction systems, including multi-Schottky junctions, semiconductor-based heterojunction-attached Schottky junctions, and multisemiconductor-based heterojunctions, is presented. Lastly, we outline future perspectives in this promising research field. This paper will assist researchers in constructing more efficient TiO-based nanoheterojunction photocatalysts.
Topics: Oxygen; Semiconductors
PubMed: 37951392
DOI: 10.1016/j.chemosphere.2023.140595 -
The artificial oxygen carrier erythrocruorin-characteristics and potential significance in medicine.Journal of Molecular Medicine (Berlin,... Aug 2023The diminishing supply and increasing costs of donated blood have motivated research into novel hemoglobin-based oxygen carriers (HBOCs) that can serve as red blood cell... (Review)
Review
The diminishing supply and increasing costs of donated blood have motivated research into novel hemoglobin-based oxygen carriers (HBOCs) that can serve as red blood cell (RBC) substitutes. HBOCs are versatile agents that can be used in the treatment of hemorrhagic shock. However, many of the RBC substitutes that are based on mammalian hemoglobins have presented key limitations such as instability and toxicity. In contrast, erythrocruorins (Ecs) are other types of HBOCs that may not suffer these disadvantages. Ecs are giant metalloproteins found in annelids, crustaceans, and some other invertebrates. Thus far, the Ecs of Lumbricus terrestris (LtEc) and Arenicola marina (AmEc) are the most thoroughly studied. Based on data from preclinical transfusion studies, it was found that these compounds not only efficiently transport oxygen and have anti-inflammatory properties, but also can be modified to further increase their effectiveness. This literature review focuses on the structure, properties, and application of Ecs, as well as their advantages over other HBOCs. Development of methods for both the stabilization and purification of erythrocruorin could confer to enhanced access to artificial blood resources.
Topics: Animals; Erythrocruorins; Oxygen; Hemoglobins; Blood Substitutes; Mammals
PubMed: 37460699
DOI: 10.1007/s00109-023-02350-3 -
Comparative Biochemistry and... Aug 2023Studies of animal physiology not only provide valuable knowledge for the species in question, but also offer insights into human physiology. This thought is best...
Studies of animal physiology not only provide valuable knowledge for the species in question, but also offer insights into human physiology. This thought is best highlighted by the 'Krogh Principle', which states "for many problems there is an animal on which it can be most conveniently studied". This graphical review focuses on three distinct stages of the oxygen transport cascade in which human exercise physiology knowledge has been enhanced by studies carried out in animal models. We begin by exploring ventilation, and the detrimental effects of cold, dry air on the airways in two sets of elite athletes, the cross-country skier and the racing sled dog. We then discuss the transport of oxygen via hemoglobin in humans and deer mice with relatively shifted oxygen dissociation curves. Finally, we consider the technical difficulties of measuring respiratory muscle blood flow in exercising humans and how an equine model can provide an understanding of the distribution of blood flow during exercise. These cases illustrate the complementary nature of physiological studies across species.
Topics: Humans; Animals; Horses; Dogs; Physiology, Comparative; Respiratory Physiological Phenomena; Models, Animal; Lung; Oxygen
PubMed: 37182787
DOI: 10.1016/j.cbpa.2023.111442 -
Cell Death & Disease Jul 2023Osteosarcoma (OS) is a common type of bone tumor for which there has been limited therapeutic progress over the past three decades. The prevalence of transcriptional...
Osteosarcoma (OS) is a common type of bone tumor for which there has been limited therapeutic progress over the past three decades. The prevalence of transcriptional addiction in cancer cells emphasizes the biological significance and clinical relevance of super-enhancers. In this study, we found that Max-like protein X (MLX), a member of the Myc-MLX network, is driven by super-enhancers. Upregulation of MLX predicts a poor prognosis in osteosarcoma. Knockdown of MLX impairs growth and metastasis of osteosarcoma in vivo and in vitro. Transcriptomic sequencing has revealed that MLX is involved in various metabolic pathways (e.g., lipid metabolism) and can induce metabolic reprogramming. Furthermore, knockdown of MLX results in disturbed transport and storage of ferrous iron, leading to an increase in the level of cellular ferrous iron and subsequent induction of ferroptosis. Mechanistically, MLX regulates the glutamate/cystine antiporter SLC7A11 to promote extracellular cysteine uptake required for the biosynthesis of the essential antioxidant GSH, thereby detoxifying reactive oxygen species (ROS) and maintaining the redox balance of osteosarcoma cells. Importantly, sulfasalazine, an FDA-approved anti-inflammatory drug, can inhibit SLC7A11, disrupt redox balance, and induce massive ferroptosis, leading to impaired tumor growth in vivo. Taken together, this study reveals a novel mechanism in which super-enhancer-driven MLX positively regulates SLC7A11 to meet the alleviated demand for cystine and maintain the redox balance, highlighting the feasibility and clinical promise of targeting SLC7A11 in osteosarcoma.
Topics: Humans; Cystine; Oxidation-Reduction; Osteosarcoma; Bone Neoplasms; Iron; Amino Acid Transport System y+; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
PubMed: 37460542
DOI: 10.1038/s41419-023-05966-y -
Biochemical Society Transactions Dec 2023SLC25A51 is the primary mitochondrial NAD+ transporter in humans and controls many local reactions by mediating the influx of oxidized NAD+. Intriguingly, SLC25A51 lacks... (Review)
Review
SLC25A51 is the primary mitochondrial NAD+ transporter in humans and controls many local reactions by mediating the influx of oxidized NAD+. Intriguingly, SLC25A51 lacks several key features compared with other members in the mitochondrial carrier family, thus its molecular mechanism has been unclear. A deeper understanding would shed light on the control of cellular respiration, the citric acid cycle, and free NAD+ concentrations in mammalian mitochondria. This review discusses recent insights into the transport mechanism of SLC25A51, and in the process highlights a multitiered regulation that governs NAD+ transport. The aspects regulating SLC25A51 import activity can be categorized as contributions from (1) structural characteristics of the transporter itself, (2) its microenvironment, and (3) distinctive properties of the transported ligand. These unique mechanisms further evoke compelling new ideas for modulating the activity of this transporter, as well as new mechanistic models for the mitochondrial carrier family.
Topics: Animals; Humans; Biological Transport; Cell Respiration; Mammals; Mitochondria; Mitochondrial Membrane Transport Proteins; NAD
PubMed: 38108469
DOI: 10.1042/BST20220318 -
The Journal of Experimental Biology Mar 2024Oxygen store management underlies dive performance and is dependent on the slow heart rate and peripheral vasoconstriction of the dive response to control tissue blood...
Oxygen store management underlies dive performance and is dependent on the slow heart rate and peripheral vasoconstriction of the dive response to control tissue blood flow and oxygen uptake. Prior research has revealed two major patterns of muscle myoglobin saturation profiles during dives of emperor penguins. In Type A profiles, myoglobin desaturated rapidly, consistent with minimal muscle blood flow and low tissue oxygen uptake. Type B profiles, with fluctuating and slower declines in myoglobin saturation, were consistent with variable tissue blood flow patterns and tissue oxygen uptake during dives. We examined arterial and venous blood oxygen profiles to evaluate blood oxygen extraction and found two primary patterns of venous hemoglobin desaturation that complemented corresponding myoglobin saturation profiles. Type A venous profiles had a hemoglobin saturation that (a) increased/plateaued for most of a dive's duration, (b) only declined during the latter stages of ascent, and (c) often became arterialized [arterio-venous (a-v) shunting]. In Type B venous profiles, variable but progressive hemoglobin desaturation profiles were interrupted by inflections in the profile that were consistent with fluctuating tissue blood flow and oxygen uptake. End-of-dive saturation of arterial and Type A venous hemoglobin saturation profiles were not significantly different, but did differ from those of Type B venous profiles. These findings provide further support that the dive response of emperor penguins is a spectrum of cardiac and vascular components (including a-v shunting) that are dependent on the nature and demands of a given dive and even of a given segment of a dive.
Topics: Animals; Spheniscidae; Diving; Myoglobin; Oxygen; Hemoglobins
PubMed: 38390686
DOI: 10.1242/jeb.246832 -
Journal of Clinical Monitoring and... Dec 2023The Oxygen Reserve Index (ORi) is an advanced plethysmography-derived variable that may help to quantify the degree of hyperoxia in patients receiving supplemental...
The Oxygen Reserve Index (ORi) is an advanced plethysmography-derived variable that may help to quantify the degree of hyperoxia in patients receiving supplemental oxygen administration. ORi is a (relative) indicator of the actual partial pressure of oxygen dissolved in arterial blood (PaO). As such, it may help in the titration of oxygen administration or it may help to warn the clinician of a deterioration of oxygen status of the patient.In this issue of the journal, Fadel et al. provide a 'classical' clinical validation study by assessing the correlation between ORi and PaO in patients about to undergo open-heart surgery. Within the moderate hyperoxic range (100-200 mmHg PaO), there is a sound correlation between ORi and PaO. This editorial discusses the clinical implications of this validation study and elaborates on the possible role of ORi monitoring in addition to SpO (peripheral arterial oxygen saturation) monitoring alone.
Topics: Humans; Oxygen; Blood Gas Analysis; Oximetry; Hyperoxia; Pulmonary Gas Exchange
PubMed: 37863861
DOI: 10.1007/s10877-023-01085-3 -
Biomolecules Jul 2023Heme is an iron-containing tetrapyrrole that plays a critical role in various biological processes, including oxygen transport, electron transport, signal transduction,... (Review)
Review
Heme is an iron-containing tetrapyrrole that plays a critical role in various biological processes, including oxygen transport, electron transport, signal transduction, and catalysis. However, free heme is hydrophobic and potentially toxic to cells. Organisms have evolved specific pathways to safely transport this essential but toxic macrocycle within and between cells. The bacterivorous soil-dwelling nematode is a powerful animal model for studying heme-trafficking pathways, as it lacks the ability to synthesize heme but instead relies on specialized trafficking pathways to acquire, distribute, and utilize heme. Over the past 15 years, studies on this microscopic animal have led to the identification of a number of heme-trafficking proteins, with corresponding functional homologs in vertebrates. In this review, we provide a comprehensive overview of the heme-trafficking proteins identified in and their corresponding homologs in related organisms.
Topics: Animals; Caenorhabditis elegans; Heme; Homeostasis; Nematoda; Biological Transport
PubMed: 37509184
DOI: 10.3390/biom13071149