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Molecular Aspects of Medicine Apr 2022Under those pathological conditions in which Myoglobin and Hemoglobin escape their cellular environments and are thus separated from cellular reductive/protective... (Review)
Review
Under those pathological conditions in which Myoglobin and Hemoglobin escape their cellular environments and are thus separated from cellular reductive/protective systems, the inherent peroxidase activities of these proteins can be expressed. This activity leads to the formation of the highly oxidizing oxo-ferryl species. Evidence that this happens in vivo is provided by the formation of a covalent bond between the heme group and the protein and this acts as an unambiguous biomarker for the presence of the oxo ferryl form. The peroxidatic activity also leads to the oxidation of lipids, the products of which can be powerful vasoconstrictive agents (e.g. isoprostanes, neuroprostanes). Here we review the evidence that lipid oxidation occurs following rhabdomyolysis and sub-arachnoid hemorrhage and that the products formed from arachidonic acid chains of phospholipids lead, through vasoconstriction, to kidney failure and brain vasospasm. Intervention in these pathological conditions through administration of reducing agents to remove ferryl heme is discussed. Through-protein electron transfer pathways that facilitate ferryl reduction at low reductant concentration have been identified. We conclude with consideration of the therapeutic use of Hemoglobin Based Oxygen carriers and how the toxicity of these may be reduced by engineering such electron transfer pathways into hemoglobin.
Topics: Heme; Hemoglobins; Humans; Myoglobin; Oxidation-Reduction; Oxygen
PubMed: 34654576
DOI: 10.1016/j.mam.2021.101045 -
Seminars in Respiratory and Critical... Oct 2023This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar-capillary interface, and the interplay among tissue perfusion,...
This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar-capillary interface, and the interplay among tissue perfusion, diffusion, and cellular respiration in the transport and utilization of oxygen. The critical interactions between oxygen and its facilitative carriers (hemoglobin in red blood cells and myoglobin in muscle cells), and with other respiratory and vasoactive molecules (carbon dioxide, nitric oxide, and carbon monoxide), are emphasized to illustrate how this versatile system dynamically optimizes regional convective transport and diffusive gas exchange. The rates of reciprocal gas exchange in the lung and the periphery must be well-matched and sufficient for meeting the range of energy demands from rest to maximal stress but not excessive as to become toxic. The mobile red blood cells play a vital role in matching tissue perfusion and gas exchange by dynamically regulating the controlled uptake of oxygen and communicating regional metabolic signals across different organs. Intracellular oxygen diffusion and facilitation via myoglobin into the mitochondria, and utilization via electron transport chain and oxidative phosphorylation, are summarized. Physiological and pathophysiological adaptations are briefly described. Dysfunction of any component across this integrated system affects all other components and elicits corresponding structural and functional adaptation aimed at matching the capacities across the entire system and restoring equilibrium under normal and pathological conditions.
Topics: Humans; Oxygen; Myoglobin; Lung; Cell Respiration; Perfusion; Oxygen Consumption
PubMed: 37541315
DOI: 10.1055/s-0043-1770061 -
Frontiers in Endocrinology 2022Primary aldosteronism (PA) is characterized by the autonomous excessive production of aldosterone in the adrenal cortex. Aldosterone is associated with damages to heart...
OBJECTIVES
Primary aldosteronism (PA) is characterized by the autonomous excessive production of aldosterone in the adrenal cortex. Aldosterone is associated with damages to heart muscle and skeletal muscle. The purpose of this study was to evaluate serum levels of muscle injury markers and their associated factors in patients with primary aldosteronism.
METHODS
We retrospectively enrolled subjects with PA and essential hypertension (EH) who had completed testing for serum high sensitivity troponin T (hs-TnT), creatine kinase isoenzyme MB (CK-MB) and myoglobin from the database of the Chongqing Primary Aldosteronism Study (CONPASS). Univariate and multivariate linear regression analyses were performed to analyze the influencing factors of myocardial injury markers.
RESULTS
In total, 278 patients with PA and 445 patients with EH were enrolled in this study. Compared with EH patients, serum concentrations of hs-TnT [7.0 (4.0-12.0) 6.0 (3.0-11.0) ng/L; =0.005] and myoglobin [24.2 (21.0-38.1) 21.8 (21.0-31.9) μg/L; =0.023] were significantly higher among PA patients, while no significant difference of CK-MB was found between two groups [1.4 (1.0-2.0) 1.3 (0.9-1.9) μg/L; =0.154]. Univariate linear regression analysis showed that myoglobin was negatively correlated with serum potassium (β=-0.31; <0.01) and positively correlated with plasma aldosterone concentration (β=0.40; <0.01) in the PA group, while no significant correlation was found between hs-TnT and biochemical parameters. After adjusting for multiple confounders, myoglobin was negatively correlated with serum potassium (β=-0.15; <0.05) and positively correlated with plasma aldosterone concentration (β=0.34; <0.01) in the PA group.
CONCLUSIONS
The serum level of myoglobin was significantly increased in PA patients, and myoglobin was independently correlated with plasma aldosterone concentration.
Topics: Aldosterone; Biomarkers; Cross-Sectional Studies; Essential Hypertension; Humans; Hyperaldosteronism; Myoglobin; Potassium; Retrospective Studies
PubMed: 35265036
DOI: 10.3389/fendo.2022.799174 -
American Journal of Physiology.... Jul 2021Myoglobin (Mb) is a regulator of O bioavailability in type I muscle and heart, at least when tissue O levels drop. Mb also plays a role in regulating cellular nitric...
Myoglobin (Mb) is a regulator of O bioavailability in type I muscle and heart, at least when tissue O levels drop. Mb also plays a role in regulating cellular nitric oxide (NO) pools. Robust binding of long-chain fatty acids and long-chain acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout (KO) mice, suggest additional roles in muscle intermediary metabolism and fuel selection. To evaluate this hypothesis, we measured energy expenditure (EE), respiratory exchange ratio (RER), body weight gain and adiposity, glucose tolerance, and insulin sensitivity in Mb knockout (Mb) and wild-type (WT) mice challenged with a high-fat diet (HFD, 45% of calories). In males ( = 10/genotype) and females ( = 9/genotype) tested at 5-6, 11-12, and 17-18 wk, there were no genotype effects on RER, EE, or food intake. RER and EE during cold (10°C, 72 h), and glucose and insulin tolerance, were not different compared with within-sex WT controls. At ∼18 and ∼19 wk of age, female Mb adiposity was ∼42%-48% higher versus WT females ( = 0.1). Transcriptomics analyses (whole gastrocnemius, soleus) revealed few consistent changes, with the notable exception of a 20% drop in soleus transferrin receptor (Tfrc) mRNA. Capillarity indices were significantly increased in Mb, specifically in Mb-rich soleus and deep gastrocnemius. The results indicate that Mb loss does not have a major impact on whole body glucose homeostasis, EE, RER, or response to a cold challenge in mice. However, the greater adiposity in female Mb mice indicates a sex-specific effect of Mb KO on fat storage and feed efficiency. The roles of myoglobin remain to be elaborated. We address sexual dimorphism in terms of outcomes in response to the loss of myoglobin in knockout mice and perform, for the first time, a series of comprehensive metabolic studies under conditions in which fat is mobilized (high-fat diet, cold). The results highlight that myoglobin is not necessary and sufficient for maintaining oxidative metabolism and point to alternative roles for this protein in muscle and heart.
Topics: Adiposity; Animals; Body Weight; Diet, High-Fat; Energy Metabolism; Fatty Acids; Female; Glucose Tolerance Test; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Myocardium; Myoglobin; Oxidation-Reduction; Phenotype; Sex Characteristics
PubMed: 33969704
DOI: 10.1152/ajpendo.00624.2020 -
Journal of Agricultural and Food... Nov 2020Appearance is an important sensory property that significantly influences consumers' perceptions of fresh meat quality. Failure to meet consumer expectations can lead to... (Review)
Review
Appearance is an important sensory property that significantly influences consumers' perceptions of fresh meat quality. Failure to meet consumer expectations can lead to rejection of meat products, concomitant loss in value, and potential production of organic waste. Immediately after animal harvest, skeletal muscle metabolism changes from aerobic to anaerobic. However, anoxic post-mortem muscle is biochemically active, and biomolecular interaction between myoglobin, mitochondria, metabolites, and lipid oxidation determines meat color. This review examines how metabolites and mitochondrial activity can influence myoglobin oxygenation and metmyoglobin reducing activity. Further, the review highlights recent research that has examined myoglobin redox dynamics, sarcoplasmic metabolite changes, and/or post-mortem biochemistry.
Topics: Animals; Color; Lipids; Meat; Muscle, Skeletal; Myoglobin; Oxidation-Reduction; Postmortem Changes
PubMed: 32045229
DOI: 10.1021/acs.jafc.9b08098 -
FASEB Journal : Official Publication of... Feb 2022GAPDH, a heme chaperone, has been previously implicated in the incorporation of heme into iNOS and soluble guanylyl cyclase (sGC). Since sGC is critical for myoglobin...
GAPDH, a heme chaperone, has been previously implicated in the incorporation of heme into iNOS and soluble guanylyl cyclase (sGC). Since sGC is critical for myoglobin (Mb) heme-maturation, we investigated the role of GAPDH in the maturation of this globin, as well as hemoglobins α, β, and γ. Utilizing cell culture systems, we found that overexpression of wild-type GAPDH increased, whereas GAPDH mutants H53A and K227A decreased, the heme content of Mb and Hbα and Hbβ. Overexpression of wild-type GAPDH fully recovered the heme-maturation inhibition observed with the GAPDH mutants. Partial rescue was observed by overexpression of sGCβ1 but not by overexpression of a sGCΔβ1 deletion mutant, which is unable to bind the sGCα1 subunit required to form the active sGCα1β1 complex. Wild type and mutant GAPDH was found to be associated in a complex with each of the globins and Hsp90. GAPDH at endogenous levels was found to be associated with Mb in differentiating C2C12 myoblasts, and with Hbγ or Hbα in differentiating HiDEP-1 erythroid progenitor cells. Knockdown of GAPDH in C2C12 cells suppressed Mb heme-maturation. GAPDH knockdown in K562 erythroleukemia cells suppressed Hbα and Hbγ heme-maturation as well as Hb dimerization. Globin heme incorporation was not only dependent on elevated sGCα1β1 heterodimer formation, but also influenced by iron provision and magnitude of expression of GAPDH, d-aminolevulinic acid, and FLVCR1b. Together, our data support an important role for GAPDH in the maturation of myoglobin and γ, β, and α hemoglobins.
Topics: Glyceraldehyde-3-Phosphate Dehydrogenases; HEK293 Cells; Heme; Hemoglobins; Humans; K562 Cells; Molecular Chaperones; Mutation, Missense; Myoglobin; Sarcoglycans
PubMed: 34972240
DOI: 10.1096/fj.202101237RR -
Comprehensive Reviews in Food Science... Jul 2023Meat color is an important aspect for the meat industry since it strongly determines the consumers' perception of product quality and thereby significantly influences... (Review)
Review
Meat color is an important aspect for the meat industry since it strongly determines the consumers' perception of product quality and thereby significantly influences the purchase decision. Emergence of new vegan meat analogs has renewed interest in the fundamental aspects of meat color in order to replicate it. The appearance of meat is based on a complex interplay between the pigment-based meat color from myoglobin and its chemical forms and light scattering from the muscle's microstructure. While myoglobin biochemistry and pigment-based meat color have been extensively studied, research on the physicochemical contribution of light scattering to meat color and the special case of structural colors causing meat iridescence has received only little attention. Former review articles focused mostly on the biochemical or physical mechanisms rather than the interplay between them, in particular the role that structural colors play. While from an economic point of view, meat iridescence might be considered negligible, an enhanced understanding of the underlying mechanisms and the interactions of light with meat microstructures can improve our overall understanding of meat color. Therefore, this review discusses both biochemical and physicochemical aspects of meat color including the origin of structural colors, highlights new color measurement methodologies suitable to investigate color phenomena such as meat iridescence, and finally presents approaches to modulate meat color in terms of base composition, additives, and processing.
Topics: Myoglobin; Iridescence; Meat; Color; Consumer Behavior
PubMed: 37306532
DOI: 10.1111/1541-4337.13191 -
European Journal of Applied Physiology Jan 2022Resting humans transport ~ 100 quintillion (10) oxygen (O) molecules every second to tissues for consumption. The final, short distance (< 50 µm) from capillary... (Review)
Review
Resting humans transport ~ 100 quintillion (10) oxygen (O) molecules every second to tissues for consumption. The final, short distance (< 50 µm) from capillary to the most distant mitochondria, in skeletal muscle where exercising O demands may increase 100-fold, challenges our understanding of O transport. To power cellular energetics O reaches its muscle mitochondrial target by dissociating from hemoglobin, crossing the red cell membrane, plasma, endothelial surface layer, endothelial cell, interstitial space, myocyte sarcolemma and a variable expanse of cytoplasm before traversing the mitochondrial outer/inner membranes and reacting with reduced cytochrome c and protons. This past century our understanding of O's passage across the body's final O frontier has been completely revised. This review considers the latest structural and functional data, challenging the following entrenched notions: (1) That O moves freely across blood cell membranes. (2) The Krogh-Erlang model whereby O pressure decreases systematically from capillary to mitochondria. (3) Whether intramyocyte diffusion distances matter. (4) That mitochondria are separate organelles rather than coordinated and highly plastic syncytia. (5) The roles of free versus myoglobin-facilitated O diffusion. (6) That myocytes develop anoxic loci. These questions, and the intriguing notions that (1) cellular membranes, including interconnected mitochondrial membranes, act as low resistance conduits for O, lipids and H-electrochemical transport and (2) that myoglobin oxy/deoxygenation state controls mitochondrial oxidative function via nitric oxide, challenge established tenets of muscle metabolic control. These elements redefine muscle O transport models essential for the development of effective therapeutic countermeasures to pathological decrements in O supply and physical performance.
Topics: Capillaries; Erythrocytes; Exercise; Humans; Mitochondria; Muscle, Skeletal; Myoglobin; Oxygen
PubMed: 34940908
DOI: 10.1007/s00421-021-04854-7 -
Nature Communications Oct 2023Gadolinium (Gd)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient...
Gadolinium (Gd)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient radiosensitization efficacy. Little attention has been given to using nanovesicles to improve its efficacy. Herein, Gd-Tex is transformed into building blocks "Gd-Tex-lipids" to self-assemble nanovesicles called Gd-nanotexaphyrins (Gd-NTs), realizing high density packing of Gd-Tex in a single nanovesicle and achieving high Gd-Tex accumulation in tumors. To elucidate the impact of O concentration on Gd-Tex radiosensitization, myoglobin (Mb) is loaded into Gd-NTs (Mb@Gd-NTs), resulting in efficient relief of tumor hypoxia and significant enhancement of Gd-Tex radiosensitization, eventually inducing the obvious long-term antitumor immune memory to inhibit tumor recurrence. In addition to Gd, the versatile Mb@Gd-NTs can also chelate Lu (Mb@Lu/Gd-NTs), enabling SPECT/MRI dual-modality imaging for accurately monitoring drug delivery in real-time. This "one-for-all" nanoplatform with the capability of chelating various trivalent metal ions exhibits broad clinical application prospects in imaging-guided radiosensitization therapy.
Topics: Humans; Gadolinium; Myoglobin; Oxygen; Radiation-Sensitizing Agents; Neoplasms; Magnetic Resonance Imaging
PubMed: 37794000
DOI: 10.1038/s41467-023-41782-w -
Biochimica Et Biophysica Acta. Reviews... May 2022Myoglobin (MB) belongs to the well-studied globin proteins superfamily. It has been extensively studied for its physiological roles in oxygen storage and transport for... (Review)
Review
Myoglobin (MB) belongs to the well-studied globin proteins superfamily. It has been extensively studied for its physiological roles in oxygen storage and transport for about a century now. However, the last two decades shed the light on unexpected aspects for MB research. Myoglobin has been suggested as a scavenger for nitric oxide and reactive oxygen species (ROS). Furthermore, MB was found to be expressed and regulated in different tissues, beyond the muscle lineage, including cancers. Current evidence suggest that MB is directly regulated by hypoxia and might be contributing to the metabolic rewiring in cancer tissues. In this article, we first discuss the MB physiological roles and then focus on the latter potential roles and regulatory networks of MB in cancer.
Topics: Humans; Hypoxia; Myoglobin; Neoplasms; Nitric Oxide; Oxygen
PubMed: 35247507
DOI: 10.1016/j.bbcan.2022.188706