scholarly journals Cardiac myoglobin deficit has evolved repeatedly in teleost fishes

2014 ◽  
Vol 10 (6) ◽  
pp. 20140225 ◽  
Author(s):  
Daniel J. Macqueen ◽  
Daniel Garcia de la serrana ◽  
Ian A. Johnston

Myoglobin (Mb) is the classic vertebrate oxygen-binding protein present in aerobic striated muscles. It functions principally in oxygen delivery and provides muscle with its characteristic red colour. Members of the Antarctic icefish family (Channichthyidae) are widely thought to be extraordinary for lacking cardiac Mb expression, a fact that has been attributed to their low metabolic rate and unusual evolutionary history. Here, we report that cardiac Mb deficit, associated with pale heart colour, has evolved repeatedly during teleost evolution. This trait affects both gill- and air-breathing species from temperate to tropical habitats across a full range of salinities. Cardiac Mb deficit results from total pseudogenization in three-spined stickleback and is associated with a massive reduction in mRNA level in two species that evidently retain functional Mb. The results suggest that near or complete absence of Mb-assisted oxygen delivery to heart muscle is a common facet of teleost biodiversity, even affecting lineages with notable oxygen demands. We suggest that Mb deficit may affect how different teleost species deal with increased tissue oxygen demands arising under climate change.

1999 ◽  
Vol 23 (2) ◽  
pp. 241-254 ◽  
Author(s):  
P White ◽  
MJ Dauncey

The genomic actions of thyroid hormones (THs) are mediated by receptors (TRs) that are encoded by two protooncogenes, c-erbA-alpha and c-erbA-beta. The precise functions of the TR isoforms are unclear and this study focuses on the potential roles of the TRalpha and TRbeta isoforms in mammalian striated muscles postnatally. The porcine TRalpha1, TRalpha2 and TRbeta1 cDNAs were first cloned, sequenced and characterised by Northern blotting. A quantitative analysis of TR isoform expression was then undertaken, using RNase protection analysis with novel riboprobes designed to detect relative expression levels of TRalpha1, TRalpha2, TRbeta1 and TRbeta2, in functionally distinct muscles from 7-week-old pigs kept under controlled conditions of nutrition and thermal environment. We found a striking muscle-specific pattern of TRalpha isoform distribution: in heart the mRNA level of TRalpha2 (non-TH binding) was markedly greater (P<0.01) than that of TRalpha1 (TH binding); in longissimus dorsi the opposite pattern of expression occurred (TRalpha1>TRalpha2, P<0.001); in soleus, diaphragm and rhomboideus there were no differences between the two isoforms. The overall abundance of TRbeta was very much lower than that of TRalpha, and TRbeta1 was expressed at a higher level than TRbeta2 in all muscles. Together with recent data from TR gene inactivation studies and the established role of TH in determining myosin heavy chain isoform expression and muscle phenotype, these results suggest a role for differential expression of TR isoforms in acquisition and maintenance of optimal cardiac and skeletal muscle function.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13545-e13545 ◽  
Author(s):  
Vladimir Konstantinovich Bozhenko ◽  
Tatyana Michailovna Kulinich ◽  
Elena Aleksandrovna Kudinova ◽  
Andrey Boldyrev ◽  
Vladimir Alekseevich Solodkij

e13545 Background: MM-D37K is a synthetic peptide which consists of p16INK4a-specific inhibitor of complex cyclin D- CDK4 and CDK6 and cell penetrating peptide (CPP) – Antp (Penetratin). We investigated in vitro and in vivo cytotoxic, cytostatic and antitumor activity of MM-D37K. The level of cyclin A, Ki67,bax, bcl-2 and pRb phosphorylation was investigated. Full range of Toxicology tests and Pharmacokinetics experiments in mice, rats and rabbits were performed. Methods: Different cell lines (Jurcat, Raji, A549, MCF-7, Hct-116, Ht-29, HEK293) were incubated with 0.1-100 mM MM-D37K for 24-48 hrs. Proliferation (MTT), DNA-content, cell cycle (flow cytometry) and mRNA level of appropriate proteins (RT PCR) were investigated. In vivo experiments were conducted on xenograft model of HCT116, A-549 at concentration 5 and 10 mg/kg of MM-D37K. Toxicology experiments were made under RF Law and included 3 types of animals. LC-MS MMD37K method of detection in plasma was developed. Results: MM-D37K prevented pRb phosphorilation and proliferation activation in all investigated cell lines. Cell cycle was blocked in G1 phase. Cytostatic effect did not depend on p16 mutation or expression. MM-D37K induced apoptosis in 20-82% of investigated cells at 40 mM with lowest level for MCF-7. LD10 for rats was 100 mg/kg and no deaths were registered for rabbits (highest dose was 50 mg/kg). Concentration of MMD-37K in plasma after 2 min and bolus i.v. injection in dose 10 mg/kg was 72.16±5.64 mcg/ml. Concentration decreased in two phases. 1st – t1/2 = 2.39±0.39 min and for 2nd t1/2=2.39±0.39 hr. Antitumor effects in xenograft model were 53% for A-549 and 67% for HCT116. Conclusions: Our results proved cytotoxic, cytostatic and antitumor effects of MM-D37K in investigated cell lines in vitro and in vivo. Toxicological and pharmacokinetics results allow us recommend for I/IIa Phase clinical trial. (Support: MetaMax Ltd., RFFI, Minpromtorg RF.)


2009 ◽  
Vol 30 (2) ◽  
pp. 181-197 ◽  
Author(s):  
Sarah L. Mincks ◽  
Patricia L. Dyal ◽  
Gordon L. J. Paterson ◽  
Craig R. Smith ◽  
Adrian G. Glover

Science ◽  
1986 ◽  
Vol 232 (4746) ◽  
pp. 90-92 ◽  
Author(s):  
DAVID W. KRAUS ◽  
JAMES M. COLACINO

An oxygen-binding hemoglobin localized in the nerves ofTellina alternata(Bivalvia) required 30 minutes to unload oxygen when excised nerves were exposed to pure nitrogen. Neural excitability under these conditions could be sustained only until deoxygenation of the hemoglobin was complete. When the oxygen-combining function of the hemoglobin was abolished with carbon monoxide, the neural excitability ceased within a few minutes of oxygen removal, a response identical to that of hemoglobinless homologous nerves of other bivalves. These results demonstrate that aerobic activity can be supported by the oxygen stored on hemoglobin in microscopic tissues for a considerable time under anoxic conditions.


1997 ◽  
Vol 273 (1) ◽  
pp. R100-R106 ◽  
Author(s):  
R. Acierno ◽  
C. Agnisola ◽  
B. Tota ◽  
B. D. Sidell

Channichthyid icefishes of Antarctica are unique among adult vertebrates. All icefish species lack hemoglobin and red blood cells in their circulating blood. All icefishes examined to date also lack the intracellular oxygen-binding protein myoglobin (Mb) in their oxidative skeletal muscles. However, some icefish species do express Mb in their heart ventricles. It is unknown whether Mb in those species in which it is present represents an evolutionary relic or has functional significance. To address this problem, we compared mechanical performance of isolated, perfused hearts from two species of icefish in which Mb is either present (Chionodraco rastrospinosus) or is absent (Chaenocephalus aceratus). Hearts were challenged with increasing afterload (2.5-4.0 kPa) under conditions of defined basal flow (approximately 100 ml.min-1.kg-1), in both the presence and absence of 5 mM sodium nitrite, a Mb poison. Unlike hearts from C. aceratus, which were unable to maintain a constant cardiac output under pressure loading, those from C. rastrospinosus retained a constant flow up to 3.5 kPa afterload. At the upper range of power outputs, hearts of Mb-lacking C. aceratus display greater oxygen utilization than those of Mb-containing C. rastrospinosus. Poisoning of Mb significantly impaired the ability of C. rastrospinosus hearts to face pressure loading without reduction in flow, whereas those of C. aceratus were refractory to the treatment. The results strongly support a functional role for Mb in the former species.


2007 ◽  
Vol 26 (5) ◽  
pp. 335-348 ◽  
Author(s):  
Antonia Rizzello ◽  
M. Antonietta Ciardiello ◽  
Raffaele Acierno ◽  
Vito Carratore ◽  
Tiziano Verri ◽  
...  

2020 ◽  
Author(s):  
Matthew R. Halley

AbstractThe “migratory revolutions” (MR) model is a synthetic theory of bird migration that seeks to explain the full range of the functional phenotype, from sedentary residents of non-seasonal (tropical) habitats to obligate long-distance migrants, as a cumulative evolutionary response to shifting distributions of adult extrinsic mortality across the annual cycle. At macroevolutionary scales, the general model predicts that migration evolves in circular patterns, reframing classic debates about the effects of migration on speciation and extinction rates. Here, I describe and apply the MR model to a well-known system, the passerine genus Catharus (Turdidae), to illustrate its broad implications for reconstructing evolutionary history.


2020 ◽  
Vol 126 (1) ◽  
pp. 129-158 ◽  
Author(s):  
Richard T. Premont ◽  
James D. Reynolds ◽  
Rongli Zhang ◽  
Jonathan S. Stamler

A continuous supply of oxygen is essential for the survival of multicellular organisms. The understanding of how this supply is regulated in the microvasculature has evolved from viewing erythrocytes (red blood cells [RBCs]) as passive carriers of oxygen to recognizing the complex interplay between Hb (hemoglobin) and oxygen, carbon dioxide, and nitric oxide—the three-gas respiratory cycle—that insures adequate oxygen and nutrient delivery to meet local metabolic demand. In this context, it is blood flow and not blood oxygen content that is the main driver of tissue oxygenation by RBCs. Herein, we review the lines of experimentation that led to this understanding of RBC function; from the foundational understanding of allosteric regulation of oxygen binding in Hb in the stereochemical model of Perutz, to blood flow autoregulation (hypoxic vasodilation governing oxygen delivery) observed by Guyton, to current understanding that centers on S-nitrosylation of Hb (ie, S-nitrosohemoglobin; SNO-Hb) as a purveyor of oxygen-dependent vasodilatory activity. Notably, hypoxic vasodilation is recapitulated by native S-nitrosothiol (SNO)–replete RBCs and by SNO-Hb itself, whereby SNO is released from Hb and RBCs during deoxygenation, in proportion to the degree of Hb deoxygenation, to regulate vessels directly. In addition, we discuss how dysregulation of this system through genetic mutation in Hb or through disease is a common factor in oxygenation pathologies resulting from microcirculatory impairment, including sickle cell disease, ischemic heart disease, and heart failure. We then conclude by identifying potential therapeutic interventions to correct deficits in RBC-mediated vasodilation to improve oxygen delivery—steps toward effective microvasculature-targeted therapies. To the extent that diseases of the heart, lungs, and blood are associated with impaired tissue oxygenation, the development of new therapies based on the three-gas respiratory system have the potential to improve the well-being of millions of patients.


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