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Journal of Inorganic Biochemistry Mar 2021Human Islet Amyloid Polypeptide (hIAPP) or amylin, can bind heme and the resultant complexes are prone to generate partially reduced oxygen species (PROS). The formation...
Human Islet Amyloid Polypeptide (hIAPP) or amylin, can bind heme and the resultant complexes are prone to generate partially reduced oxygen species (PROS). The formation of PROS and the related oxidative stress highlight the importance of Heme-hIAPP in the onset and development of Type 2 Diabetes mellitus (T2Dm) in humans. In this study, the interaction of Heme-hIAPP with apomyoglobin (ApoMb) has been investigated using a combination of spectroscopic and electrophoresis techniques. Absorption, resonance Raman data and gel electrophoresis results confirm that ApoMb can uptake heme from Heme-hIAPP and constitute a six-coordinate high-spin ferric heme active site identical to that of myoglobin (Mb). The heme transfer reaction has two distinct kinetic steps. A possible mechanism of this reaction involves heme transfer to the apoprotein in the first step followed by a reorganisation of the protein chain to form the active site of native Mb. Increase in the pH of the reaction medium enhances the rate of the second step of heme transfer. This possibly corresponds to the deprotonation of a propionate side chain of the heme moiety at high pH which facilitates secondary interactions with the conserved distal Lys45 residue of horse heart Mb. Additionally, ApoMb sequesters ligand bound heme from Heme-hIAPP. After the heme transfer reaction, the amount of PROS formed by Heme-hIAPP complex diminishes significantly. This not only potentially diminishes heme-induced toxicity in the pancreatic β-cells but also produces Mb which has well-documented functions throughout the respiratory system and can thereby likely reduce the risks associated with T2Dm.
Topics: Animals; Heme; Humans; Islet Amyloid Polypeptide; Myoglobin
PubMed: 33450674
DOI: 10.1016/j.jinorgbio.2020.111348 -
Marine Genomics Feb 2020The ancient origins and functional versatility of globins make them ideal subjects for studying physiological adaptation to environmental change. Our goals in this... (Review)
Review
The ancient origins and functional versatility of globins make them ideal subjects for studying physiological adaptation to environmental change. Our goals in this review are to describe the evolution of the vertebrate globin gene superfamily and to explore the structure/function relationships of hemoglobin, myoglobin, neuroglobin and cytoglobin in teleost fishes. We focus on the globins of Antarctic notothenioids, emphasizing their adaptive features as inferred from comparisons with human proteins. We dedicate this review to Guido di Prisco, our co-author, colleague, friend, and husband of C.V. Ever thoughtful, creative, and enthusiastic, Guido spearheaded study of the structure, function, and evolution of the hemoglobins of polar fishes - this review is testimony to his wide-ranging contributions. Throughout his career, Guido inspired younger scientists to embrace polar biological research, and he challenged researchers of all ages to explore evolutionary adaptation in the context of global climate change. Beyond his scientific contributions, we will miss his warmth, his culture, and his great intellect. Guido has left an outstanding legacy, one that will continue to inspire us and our research.
Topics: Adaptation, Physiological; Amino Acid Sequence; Animals; Antarctic Regions; Cytoglobin; Evolution, Molecular; Fishes; Globins; Hemoglobins; Multigene Family; Myoglobin; Neuroglobin; Synteny
PubMed: 31735579
DOI: 10.1016/j.margen.2019.100724 -
Archives of Pathology & Laboratory... Nov 2019Urine myoglobin testing is primarily indicated for diagnosis and risk assessment of kidney injury in patients with rhabdomyolysis. However, its utility is limited by a... (Observational Study)
Observational Study
CONTEXT.—
Urine myoglobin testing is primarily indicated for diagnosis and risk assessment of kidney injury in patients with rhabdomyolysis. However, its utility is limited by a lack of rapid and reliable results. Myoglobin reacts positively for blood by urine dipstick, which can serve as an indicator of myoglobinuria.
OBJECTIVE.—
To evaluate the performance and value of blood and red cell measurements by urinalysis as a surrogate test for myoglobinuria in routine clinical practice.
DESIGN.—
This study is a retrospective observational study involving analysis of hemoglobin and red blood cell results by urinalysis in patients tested for urine myoglobin.
RESULTS.—
A total of 13 139 urine myoglobin results from 88 Veterans Affairs facilities during a 15-year period ending in October 2014 were evaluated. Among methods used by each laboratory, qualitative urine myoglobin tests declined from 25 of 53 (47.1%) in 2000 to 5 of 77 (6.4%) in 2013. Of 7311 tests (55.6%) performed by quantitative methods with concomitant urinalysis, 3915 (53.5%) showed negative to trace blood results, of which myoglobin was 1000 μg/L or greater in 17 (0.4%). Among 1875 (25.5%) with 3+ (large) blood results, urine myoglobin was ≥1000 μg/L in 273 of 1533 (17.8%) with hematuria (≥5 red blood cells per microliter) and 109 of 342 (31.9%) without hematuria.
CONCLUSIONS.—
Urinalysis results reliably predicted the absence of myoglobinuria and could be used to avert overtesting for urine myoglobin while also providing useful diagnostic information when urine myoglobin test results are not immediately available.
Topics: Evidence-Based Practice; Hematuria; Hemoglobins; Humans; Myoglobin; Myoglobinuria; Retrospective Studies; Rhabdomyolysis; United States; United States Department of Veterans Affairs; Urinalysis
PubMed: 31116043
DOI: 10.5858/arpa.2018-0475-OA -
ELife Jun 2023The reasons for poor healing of pressure injuries are poorly understood. Vascular ulcers are worsened by extracellular release of hemoglobin, so we examined the impact...
The reasons for poor healing of pressure injuries are poorly understood. Vascular ulcers are worsened by extracellular release of hemoglobin, so we examined the impact of myoglobin (Mb) iron in murine muscle pressure injuries (mPI). Tests used Mb-knockout or treatment with deferoxamine iron chelator (DFO). Unlike acute injuries from cardiotoxin, mPI regenerated poorly with a lack of viable immune cells, persistence of dead tissue (necro-slough), and abnormal deposition of iron. However, Mb-knockout or DFO-treated mPI displayed a reversal of the pathology: decreased tissue death, decreased iron deposition, decrease in markers of oxidative damage, and higher numbers of intact immune cells. Subsequently, DFO treatment improved myofiber regeneration and morphology. We conclude that myoglobin iron contributes to tissue death in mPI. Remarkably, a large fraction of muscle death in untreated mPI occurred later than, and was preventable by, DFO treatment, even though treatment started 12 hr after pressure was removed. This demonstrates an opportunity for post-pressure prevention to salvage tissue viability.
Topics: Mice; Humans; Animals; Iron; Deferoxamine; Myoglobin; Pressure Ulcer; Necrosis; Muscles
PubMed: 37267120
DOI: 10.7554/eLife.85633 -
Meat Science Jul 2022The objective of this study was to determine the extent that myoglobin and beef color are associated with calpain-1 relative abundance relative and tenderness....
The objective of this study was to determine the extent that myoglobin and beef color are associated with calpain-1 relative abundance relative and tenderness. Longissimus lumborum (LL) samples from the left side of Holstein beef carcasses (n = 31) were collected immediately post-evisceration for 0 h analyses. At 48 h postmortem six steaks were removed from the right side of each carcass for analyses at 48 and 336 h postmortem. Myoglobin concentrations resulted in negative correlations (P < 0.05) to Warner-Bratzler shear force (WBSF) values at 336 h postmortem. L*, a*, and b* values at 48 h resulted in positive correlations (P < 0.05) with WBSF values at 48 and 336 h. Values for b* at 336 h had positive correlations with calpain-1 concentration at 0 and 336 h. Data from this study indicate a potential relationship between myoglobin concentration and meat color with tenderness aspects and calpain-1 relative abundance.
Topics: Cattle; Animals; Female; Muscle, Skeletal; Calpain; Myoglobin; Meat
PubMed: 35472686
DOI: 10.1016/j.meatsci.2022.108824 -
Journal of the Science of Food and... Nov 2019The Arctic muskox has economic potential as an alternative meat species and is becoming increasingly popular. The present study aimed to determine the primary structure... (Comparative Study)
Comparative Study
BACKGROUND
The Arctic muskox has economic potential as an alternative meat species and is becoming increasingly popular. The present study aimed to determine the primary structure and pseudoperoxidase activity of muskox myoglobin (Mb) compared to cattle and water buffalo myoglobins.
RESULTS
The primary structure of muskox Mb was determined via a matrix-assisted laser desorption ionization-time of flight mass spectrometry-based mapping approach using the sheep Mb as a reference sequence. The muskox Mb consists of 153 amino acid residues and shows 100% identity with sheep Mb, whereas 98.69% and 97.38% identity is found with cattle and water buffalo Mbs, respectively. Muskox Mb has an autoxidation rate (MetMb formation) higher than both cattle and water buffalo Mbs at pH 7.2 (37 °C). Moreover, its pseudoperoxidase activity is higher than both cattle and water buffalo Mbs at pH 7.4 (physiological pH), whereas it is slightly lower than cattle Mb and higher than water buffalo at a lower pH (5.8), corresponding to the conditions in meat.
CONCLUSION
For the first time, the present study reports the purification of myoglobin from muskoxen and, furthermore, a comparative study is conducted on autoxidation and pseudoperoxidase activity with respect to cattle and water buffalo Mbs at both physiological and acid pH. Overall, the results of the current research provide novel information for future studies useful to the meat industry when considering the importance of myoglobin as a principal pigment in meat colour stability. © 2019 Society of Chemical Industry.
Topics: Amino Acid Sequence; Animals; Buffaloes; Cattle; Color; Hydrogen-Ion Concentration; Kinetics; Mass Spectrometry; Meat; Myoglobin; Sequence Alignment; Sheep
PubMed: 31259416
DOI: 10.1002/jsfa.9901 -
Cells Sep 2023Brown adipose tissue (BAT) plays an important role in energy homeostasis by generating heat from chemical energy via uncoupled oxidative phosphorylation. Besides its... (Review)
Review
Brown adipose tissue (BAT) plays an important role in energy homeostasis by generating heat from chemical energy via uncoupled oxidative phosphorylation. Besides its high mitochondrial content and its exclusive expression of the uncoupling protein 1, another key feature of BAT is the high expression of myoglobin (MB), a heme-containing protein that typically binds oxygen, thereby facilitating the diffusion of the gas from cell membranes to mitochondria of muscle cells. In addition, MB also modulates nitric oxide (NO•) pools and can bind C16 and C18 fatty acids, which indicates a role in lipid metabolism. Recent studies in humans and mice implicated MB present in BAT in the regulation of lipid droplet morphology and fatty acid shuttling and composition, as well as mitochondrial oxidative metabolism. These functions suggest that MB plays an essential role in BAT energy metabolism and thermogenesis. In this review, we will discuss in detail the possible physiological roles played by MB in BAT thermogenesis along with the potential underlying molecular mechanisms and focus on the question of how BAT-MB expression is regulated and, in turn, how this globin regulates mitochondrial, lipid, and NO• metabolism. Finally, we present potential MB-mediated approaches to augment energy metabolism, which ultimately could help tackle different metabolic disorders.
Topics: Humans; Animals; Mice; Myoglobin; Adiposity; Obesity; Adipose Tissue, Brown; Cell Membrane; Fatty Acids
PubMed: 37759463
DOI: 10.3390/cells12182240 -
Experimental Biology and Medicine... Jul 2022Severe coronavirus (SARS-COV-2) infection often leads to systemic inflammation accompanied by cardiovascular complications including venous thromboembolism (VTE)....
Severe coronavirus (SARS-COV-2) infection often leads to systemic inflammation accompanied by cardiovascular complications including venous thromboembolism (VTE). However, it is largely undefined if inflammatory markers such as lipocalin-2 (LNC2), calprotectin (S100A8/A9), and cystatin C (CST3), previously linked with VTE, play roles in cardiovascular complications and advancement of COVID-19 severity. To investigate the same, hospitalized moderate and severe (presented pneumonia and required intensive care) COVID-19 patients were recruited. The levels of plasma LNC2, S100A8/A9, CST3, myoglobin, and cardiac Troponin I (cTnI) were assessed through enzyme-linked immunosorbent assay (ELISA). The investigation revealed a significantly upregulated level of plasma LNC2 at the moderate stage of SARS-CoV-2 infection. In contrast, the levels of S100A8/A9 and CST3 in moderate patients were comparable to healthy controls; however, a profound induction was observed only in severe COVID-19 patients. The tissue injury marker myoglobin was unchanged in moderate patients; however, a significantly elevated level was observed in the critically ill COVID-19 patients. In contrast, cTnI level was unchanged both in moderate and severe patients. Analysis revealed a positive correlation between the levels of S100A8/A9 and CST3 with myoglobin in COVID-19. In silico analysis predicted interactions of S100A8/A9 with toll-like receptor 4 (TLR-4), MyD88 LY96, and LCN2 with several other inflammatory mediators including MMP2, MMP9, TIMP1, and interleukins (IL-6, IL-17A, and IL-10). In summary, early induction of LCN2 likely plays a role in advancing the COVID-19 severity. A positive correlation of S100A8/A9 and CST3 with myoglobin suggests that these proteins may serve as predictive biomarkers for thromboembolism and tissue injury in COVID-19.
Topics: Biomarkers; COVID-19; Calgranulin A; Calgranulin B; Cystatin C; Humans; Lipocalin-2; Myoglobin; SARS-CoV-2; Venous Thromboembolism
PubMed: 35466734
DOI: 10.1177/15353702221091990 -
Analytical and Bioanalytical Chemistry Aug 2019Isoelectric focusing (IEF), a powerful technique for protein separation and enrichment, was successfully integrated into microfluidic paper-based analytical devices...
Isoelectric focusing (IEF), a powerful technique for protein separation and enrichment, was successfully integrated into microfluidic paper-based analytical devices (μPADs) in this work. The μPADs for isoelectric focusing were fabricated by octadecyltrichlorosilane (OTS) silanization and subsequent region-selective plasma treatment. The system of IEF on μPADs could be easily assembled. And a series of conditions of the system were investigated, including the suitable concentration of ampholyte to create good pH gradient, the effect of polyvinylpyrrolidone (PVP) on electroosmotic flow (EOF) suppression, and focusing voltage applied on the paper channel. After optimization, simultaneous separation and enrichment of protein sample containing myoglobin and cytochrome C was successfully demonstrated. Besides, parallel IEF on multichannels were also achieved for the separation of multiple protein samples on one single chip, and their performance was compared with that of the conventional gel-IEF system. The developed IEF on μPADs exhibits appealing features such as low cost, simplicity, and disposability and are believed to have great application potentials.
Topics: Cytochromes c; Electroosmosis; Hydrogen-Ion Concentration; Isoelectric Focusing; Microfluidic Analytical Techniques; Myoglobin; Paper; Povidone; Silanes
PubMed: 31317237
DOI: 10.1007/s00216-019-02008-5 -
International Journal of Environmental... Aug 2022The aim of this study was to determine if 1 h after a cycling race, changes in plasma creatine kinase activity (CK) and myoglobin concentrations (MB) differ between...
The aim of this study was to determine if 1 h after a cycling race, changes in plasma creatine kinase activity (CK) and myoglobin concentrations (MB) differ between mountain bike and road cyclists and if these changes show any correlation with race performance. Male mountain bike cyclists ( = 11) under 23 years old and male road cyclists ( = 14), also under 23 years old, were studied following one of their respective races. The cyclists had blood drawn 2 h before and 1 h after the race to assess CK and MB, then the change in pre- and post-race difference was calculated (ΔCK and ΔMB). Each cyclist's performance time was recorded and the time difference from the winner was calculated (T). The cyclists' aerobic capacity was assessed during the incremental test, which determines maximal oxygen uptake and maximal aerobic power. It was observed that 1 h after the cycling race, CK ( = 0.001, = 0.40, = 15.6) and MB ( = 0.000, = 0.43, = 17.2) increased, compared to pre-race values. Post-race CK increased only in road cyclists, while post-race MB increased only in mountain bike cyclists. Smaller T were found for lower ΔMB in road cyclists but for higher ΔCK in mountain bike cyclists.
Topics: Adult; Bicycling; Creatine Kinase; Exercise Tolerance; Humans; Male; Myoglobin; Young Adult
PubMed: 35954814
DOI: 10.3390/ijerph19159456